Background <p>The effectiveness of nutritional supplements is controversial compared to standard supplementation in the clinical management of individuals with acute pancreatitis (AP). We performed a network meta-analysis (NMA) to compare and rank their efficacy.</p> Methods <p>Four databases (Web of Science, Cochrane, Embase, PubMed) were searched for randomized controlled trials. Random-effects models to derive outcome estimates, with risk ratios (RRs) and 95% confidence intervals (CIs) calculated for each comparison. The surface under the cumulative ranking (SUCRA) was used to rank the relative efficacy of all therapies.</p> Results <p>Seventeen trials including 1,313 patients were analyzed. ω-3 fatty acid supplementation emerged as the most effective intervention. It significantly shortened hospital stay (mean difference = -5.82 days; 95% CI -10.62 to -1.01) and intensive care unit (ICU) stay (mean difference = -6.09 days; 95% CI -8.98 to -3.20). It also reduced ICU stay in patients with severe acute pancreatitis (SAP) (mean difference = -6.09 days; 95% CI -8.98 to -3.02). Moreover, ω-3 fatty acids reduced the risk of sepsis (RR = 0.35; 95% CI 0.14–0.89) in AP and SAP (RR = 0.30; 95% CI 0.10–0.93). Synbiotics dramatically reduced the incidence of bacteremia (RR = 0.27; 95% CI = 0.09–0.86). It also reduced ICU stay with the enteral route (mean difference = -3.22 days; 95% CI, -3.95 to -2.49). However, none of the regimens produced significant improvements in mortality, infectious complications, time to oral feeding, or multiorgan failure (MOF).</p> Conclusions <p>This NMA preliminary suggests that ω-3 fatty acid supplementation demonstrates the greatest efficacy in reducing the length of hospital and ICU stays in individuals with AP. Hence, it should be considered for routine use in AP, as it may reduce the future medical burden. Furthermore, increasing ω-3 fatty acids and synbiotics may contribute to a reduced incidence of sepsis and bacteremia, respectively.</p>