Diagnosing acute cholecystitis (AC) in patients with end-stage renal disease (ESRD) is challenging because chronic systemic inflammation and immune dysregulation may obscure acute inflammatory responses. Conventional inflammatory markers may therefore have limited diagnostic specificity in this population. This study aimed to evaluate the diagnostic utility of systemic inflammatory indices in ESRD patients undergoing cholecystectomy. This retrospective single-center study included 48 ESRD patients who underwent cholecystectomy either for clinically suspected AC (AC group, n = 31) or prophylactically prior to kidney transplantation (RT group, n = 17). Demographic characteristics and laboratory parameters were obtained from preoperative blood tests. Systemic inflammatory indices, including the neutrophil-to-lymphocyte ratio, systemic immune-inflammation index, systemic inflammation response index (SIRI), and pan-immune-inflammation value (PIV), were calculated. Histopathological findings were used as the reference standard for confirming acute inflammation. Exploratory receiver operating characteristic curve analysis was performed to evaluate diagnostic performance and determine optimal cutoff values. Histopathological examination demonstrated neutrophilic infiltration consistent with acute inflammation in 30% of patients with clinically suspected AC. Compared with the RT group, patients with histopathologically confirmed acute inflammation had significantly higher neutrophil counts and PIV levels and lower serum albumin levels. In receiver operating characteristic analysis comparing histopathologically confirmed acute cases with RT controls, PIV showed the highest diagnostic accuracy (area under the curve [AUC] = 0.771), followed by C-reactive protein (AUC = 0.733) and SIRI (AUC = 0.732). Within the AC cohort, SIRI demonstrated the best discriminatory ability for differentiating acute from chronic inflammatory changes (AUC = 0.732). Optimal cutoff values differed substantially between analyses, with lower thresholds observed when acute cases were compared with RT controls and higher thresholds required within the AC cohort. Composite inflammatory indices, particularly SIRI and PIV, may provide additional information in identifying histopathologically confirmed acute inflammation in ESRD patients. However, given the limited sample size, these findings should be interpreted as exploratory and require validation in larger prospective studies.