The therapeutic potential of L-sodium lactate was investigated in a dextran sodium sulfate (DSS)-induced colitis model. Treatment with L-sodium lactate significantly mitigated disease severity, as evidenced by reduced colon shortening (P < 0.05) and elevated levels of the anti-inflammatory cytokine IL-10 (P < 0.05). Tandem mass tag (TMT)-based proteomic profiling revealed dual mechanisms, including the upregulation of cell cycle- and proliferation-associated proteins (PCNA, SMC, eEF2K) and the downregulation of immune-related proteins (immunoglobulin variants, Granzyme A). In vitro, 10 μM L-sodium lactate promoted the proliferation and migration of colorectal cancer cells (MC38/HCT116)(P < 0.05),accompanied by increased expression of c-Myc and PCNA. Collectively, these findings identify L-sodium lactate as a key metabolite that enhances mucosal repair while suppressing inflammation.