DW1029M is a botanical extract consisting of Morus bark (MB) and Puerariae radix (PR), produced by Dong-Wha Pharmaceutical, Inc. Co. for nephroprotective drug development; it has been in phase II clinical trials in Korea. In our mechanistic investigations, we found that DW1029M inhibits advanced glycation end products (AGEs), rat lens aldose reductase (RLAR), and transforming growth factor β1(TGFβ1) signaling, all of which are implicated in diabetic complications such as diabetic nephropathy and diabetic retinopathy. DW1029M inhibits AGE formation via Fe2+ ion chelation. The extract contains 13 active constituents that inhibit AGE formation, eight that inhibit RLAR activity, and one inhibitor of TGFβ1 signaling. Our results suggest DW1029M protects against diabetic nephropathy via blockade of AGE formation, RLAR activity, and TGFβ1 signaling.