Objective. This study aimed to delve into the antioxidant potential of small-molecule peptides derived from Lactiplantibacillus plantarum SCS2 (L. plantarum SCS2), targeting hydrogen peroxide- (H2O2-) induced rat insulinoma (INS-1) cells. Methods. INS-1 cells were pretreated with small-molecule peptides of distinct molecular weights, specifically P1 (≤1 kDa), P2 (1–5 kDa), and P3 (5–10 kDa), which were isolated from L. plantarum SCS2, followed by H2O2 to induce oxidative damage in INS-1 cells. The oxidative status of the cells was assessed by measuring reactive oxygen species (ROS), malondialdehyde (MDA) concentrations, and antioxidant enzyme activities. In addition, the expression levels of proteins and genes associated with the Kelch-like ECH-associated protein 1 (Keap1)-Nuclear factor erythroid 2-related factor 2 (Nrf2) pathway were examined to elucidate the underlying antioxidative mechanisms of the small-molecule peptides from L. plantarum SCS2. Results. The cellular activity and the activities of antioxidant enzymes, such as superoxide dismutase, catalase, and glutathione peroxidase, were higher after pretreatment with P1 than those after pretreatment with P2 and P3, which led to the suppression of ROS and MDA production. In addition, P1 upregulated mRNA and protein expression of Nrf2 and heme oxygenase-1, significantly decreased mRNA and protein expression of Keap1, and promoted the entry of Nrf2 into the nucleus compared with that in the model group. Conclusion. P1 from L. plantarum SCS2 could activate the Keap1-Nrf2 signaling pathway, thereby ameliorating oxidative damage in INS-1 cells.