diff --git a/source/blender/blenkernel/intern/customdata.cc b/source/blender/blenkernel/intern/customdata.cc
index 55898872224..fcee9ab4c71 100644
--- a/source/blender/blenkernel/intern/customdata.cc
+++ b/source/blender/blenkernel/intern/customdata.cc
@@ -2155,6 +2155,8 @@ static const LayerTypeInfo LAYERTYPEINFO[CD_NUMTYPES] = {
      layerDefault_propquaternion},
 };
 
+static_assert(sizeof(mat4x4f) == sizeof(blender::float4x4));
+
 static const char *LAYERTYPENAMES[CD_NUMTYPES] = {
     /*   0-4 */ "CDMVert",
     "CDMSticky",
diff --git a/source/blender/blenloader/intern/readfile.cc b/source/blender/blenloader/intern/readfile.cc
index 2c461775696..164948e44f7 100644
--- a/source/blender/blenloader/intern/readfile.cc
+++ b/source/blender/blenloader/intern/readfile.cc
@@ -1825,7 +1825,8 @@ static void *read_struct(FileData *fd, BHead *bh, const char *blockname)
       }
       else {
         /* SDNA_CMP_EQUAL */
-        temp = MEM_mallocN(bh->len, blockname);
+        const int alignment = DNA_struct_alignment(fd->filesdna, bh->SDNAnr);
+        temp = MEM_mallocN_aligned(bh->len, alignment, blockname);
 #ifdef USE_BHEAD_READ_ON_DEMAND
         if (BHEADN_FROM_BHEAD(bh)->has_data) {
           memcpy(temp, (bh + 1), bh->len);
diff --git a/source/blender/makesdna/DNA_genfile.h b/source/blender/makesdna/DNA_genfile.h
index c277fdd1ad5..374f3dafbc7 100644
--- a/source/blender/makesdna/DNA_genfile.h
+++ b/source/blender/makesdna/DNA_genfile.h
@@ -190,6 +190,11 @@ int DNA_struct_member_size(const struct SDNA *sdna, short type, short name);
  */
 int DNA_elem_type_size(eSDNA_Type elem_nr);
 
+/**
+ * Get the alignment that should be used when allocating memory for this type.
+ */
+int DNA_struct_alignment(const struct SDNA *sdna, int struct_nr);
+
 /**
  * Rename a struct
  */
diff --git a/source/blender/makesdna/DNA_sdna_types.h b/source/blender/makesdna/DNA_sdna_types.h
index 4dc216204e5..ad2ff9e5049 100644
--- a/source/blender/makesdna/DNA_sdna_types.h
+++ b/source/blender/makesdna/DNA_sdna_types.h
@@ -80,6 +80,13 @@ typedef struct SDNA {
     /** A version of #SDNA.structs_map that uses #SDNA.alias.types for its keys. */
     struct GHash *structs_map;
   } alias;
+
+  /**
+   * Alignment used when allocating pointers to this type. The actual minimum alignment of the
+   * type may be lower in some cases. For example, the pointer alignment of a single char is at
+   * least 8 bytes, but the alignment of the type itself is 1.
+   */
+  int *types_alignment;
 } SDNA;
 
 #
diff --git a/source/blender/makesdna/DNA_vec_types.h b/source/blender/makesdna/DNA_vec_types.h
index ba98dadf16b..d3023d5c432 100644
--- a/source/blender/makesdna/DNA_vec_types.h
+++ b/source/blender/makesdna/DNA_vec_types.h
@@ -50,6 +50,11 @@ typedef struct vec4f {
   float x, y, z, w;
 } vec4f;
 
+/**
+ * This type generally shouldn't be used. It only exists for cases where a DNA type that
+ * corresponds to `blender:float4x4` is required. Note that `float4x4` is 16 byte aligned, but we
+ * can't enforce that this struct yet.
+ */
 typedef struct mat4x4f {
   float value[4][4];
 } mat4x4f;
diff --git a/source/blender/makesdna/intern/dna_genfile.cc b/source/blender/makesdna/intern/dna_genfile.cc
index 885c882ba4b..5ddcdb7c571 100644
--- a/source/blender/makesdna/intern/dna_genfile.cc
+++ b/source/blender/makesdna/intern/dna_genfile.cc
@@ -21,6 +21,7 @@
 #include "MEM_guardedalloc.h" /* for MEM_freeN MEM_mallocN MEM_callocN */
 
 #include "BLI_endian_switch.h"
+#include "BLI_math_matrix_types.hh"
 #include "BLI_memarena.h"
 #include "BLI_string.h"
 #include "BLI_utildefines.h"
@@ -132,6 +133,7 @@ void DNA_sdna_free(SDNA *sdna)
   MEM_freeN((void *)sdna->names_array_len);
   MEM_freeN((void *)sdna->types);
   MEM_freeN(sdna->structs);
+  MEM_freeN(sdna->types_alignment);
 
 #ifdef WITH_DNA_GHASH
   if (sdna->structs_map) {
@@ -522,6 +524,19 @@ static bool init_structDNA(SDNA *sdna, bool do_endian_swap, const char **r_error
     sdna->names_array_len = names_array_len;
   }
 
+  sdna->types_alignment = static_cast<int *>(
+      MEM_malloc_arrayN(sdna->types_len, sizeof(int), __func__));
+  for (int i = 0; i < sdna->types_len; i++) {
+    sdna->types_alignment[i] = int(__STDCPP_DEFAULT_NEW_ALIGNMENT__);
+  }
+  {
+    uint dummy_index = 0;
+    /* TODO: This should be generalized at some point. We should be able to specify overaligned
+     * types directly in the DNA struct definitions. */
+    sdna->types_alignment[DNA_struct_find_without_alias_ex(sdna, "mat4x4f", &dummy_index)] =
+        alignof(blender::float4x4);
+  }
+
   return true;
 }
 
@@ -1265,7 +1280,9 @@ void *DNA_struct_reconstruct(const DNA_ReconstructInfo *reconstruct_info,
   const SDNA_Struct *new_struct = newsdna->structs[new_struct_nr];
   const int new_block_size = newsdna->types_size[new_struct->type];
 
-  char *new_blocks = static_cast<char *>(MEM_callocN(blocks * new_block_size, "reconstruct"));
+  const int alignment = DNA_struct_alignment(newsdna, new_struct_nr);
+  char *new_blocks = static_cast<char *>(
+      MEM_calloc_arrayN_aligned(new_block_size, blocks, alignment, "reconstruct"));
   reconstruct_structs(reconstruct_info,
                       blocks,
                       old_struct_nr,
@@ -1697,6 +1714,11 @@ int DNA_elem_type_size(const eSDNA_Type elem_nr)
   return 8;
 }
 
+int DNA_struct_alignment(const SDNA *sdna, const int struct_nr)
+{
+  return sdna->types_alignment[struct_nr];
+}
+
 /* -------------------------------------------------------------------- */
 /** \name Version Patch DNA
  * \{ */