Background Surgical site infection (SSI), albeit infrequent, drastically impacts the quality of care. This article endeavors to investigate the predictive factors of SSIs following surgical interventions that involve the gastrointestinal (GI) tract within a single institution in a resource-limited setting. Methods Over seven years from June 2015 to June 2022, patients who underwent GI surgery and developed SSI were retrospectively matched with an unaffected case-control cohort of patients. Standardized techniques for wound culture, laboratory evaluation of bacterial isolates, and antibiotic susceptibility tests were employed. Logistic regression analysis was utilized to investigate the predictive factors associated with 30-day postoperative SSI occurrence. Results A total of 525 patients who underwent GI surgical procedures were included, among whom, 86 (16.4%) developed SSI and the majority of SSIs were superficial (74.4%). Escherichia coli was the most commonly isolated bacterium (54.4%), and a high percentage of multidrug-resistant organisms were observed (63.8%). In multivariate Cox regression analysis, illiteracy (Odds ratio [OR]:40.31; 95% confidence interval [CI]: 9.54-170.26), smoking (OR: 21.15; 95% CI: 4.63-96.67), diabetes (OR: 5.07; 95% CI: 2.27-11.35), leukocytosis (OR: 2.62; 95% CI: 1.24-5.53), hypoalbuminemia (OR: 3.70; 95% CI: 1.35-10.16), contaminated and dirty wounds (OR: 6.51; 95% CI:1.62-26.09), longer operation duration (OR: 1.02; 95% CI: 1.01-1.03), emergency operations (OR: 12.58; 95% CI: 2.91-54.30), and extending antibiotic prophylaxis duration (OR: 3.01; 95% CI: 1.28-7.10) were the independent risk factors for SSI (all p < 0.05). Conclusions This study highlights significant predictors of SSI, including illiteracy, smoking, diabetes, leukocytosis, hypoalbuminemia, contaminated and dirty wounds, longer operative time, emergency operations, and extending antibiotic prophylaxis duration. Identifying these risk factors can help surgeons adopt appropriate measures to reduce postoperative SSI and improve the quality of surgical care, especially in a resource-limited setting with no obvious and strict policy for reducing SSI.