Introduction: Postoperative peritoneal adhesion is a common complication that can lead to severe morbidity, including chronic pain and intestinal obstruction. Adhesion formation involves an imbalance between proliferation and apoptosis of mesothelial cells, with suppression of caspase-3 activity playing a key role. Quercetin has been suggested to possess anti-adhesion potential through caspase-3 activation; however, experimental evidence supporting this mechanism remains limited. This study aims to evaluate the effect of intraperitoneal quercetin administration on caspase-3 levels and peritoneal adhesion formation in a Wistar rat (Rattus norvegicus) model following laparotomy. Methods: This true experimental study employed a posttest-only control design involving 36 healthy male Wistar rats aged 3–4 months and weighing 200–250 g. The animals were randomly allocated into two groups: control (normal saline irrigation) and treatment (intraperitoneal quercetin at 50 mg/kg body weight). Peritoneal adhesion was induced by standardized peritoneal abrasion. On post-operative day 7, evaluations included caspase-3 level measurement using ELISA and macroscopic adhesion grading with a validated scoring system. Statistical analysis was performed using the Mann–Whitney test. Results: Caspase-3 concentration in the quercetin-treated group was significantly higher than in the control group (2.968 ± 0.970 vs. 1.277 ± 0.482; p = 0.000), indicating enhanced apoptosis. The mean adhesion score was significantly lower in the quercetin group (1.280 ± 1.127 vs. 2.220 ± 1.047; p = 0.012), demonstrating a protective effect of quercetin against pathological adhesion formation. Conclusion: Intraperitoneal quercetin significantly reduces peritoneal adhesion formation and is associated with increased caspase-3 levels, suggesting a potential apoptosis-related mechanism. These findings support further investigation into its clinical applicability, including optimization of dosing, safety evaluation, and integration into perioperative pharmacotherapy protocols. If validated in human studies, quercetin may contribute to reducing surgical complications and associated healthcare burdens.