This study aimed to evaluate the anti-inflammatory effects of pork-derived digestive hydrolysates and explore their underlying mechanisms. Pork meat was subjected to simulated gastrointestinal digestion and fractionated into different molecular weight fractions. Cytotoxicity assessment using RAW264.7 macrophages revealed no significant cytotoxic effects in any of the treatment groups. Treatment with pork hydrolysates significantly reduced the production of nitric oxide (NO) and pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β), in a dose-dependent manner. In addition, both mRNA and protein expression levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were markedly suppressed, with the <5 kDa fraction showing the most pronounced effects. Furthermore, the hydrolysates significantly inhibited the phosphorylation of mitogen-activated protein kinases (MAPKs), specifically c-Jun N-terminal kinase (JNK) and p38, indicating the regulation of inflammatory signaling pathways. Taken together, these results suggest that pork-derived digestive hydrolysates, particularly the low-molecular-weight fraction (<5 kDa), may exhibit anti-inflammatory effects by suppressing MAPK signaling pathways and downstream inflammatory mediators. These findings suggest that pork-derived hydrolysates, particularly the low-molecular-weight fraction (<5 kDa), may possess in vitro anti-inflammatory potential through the modulation of inflammatory signaling pathways.