Laparotomy remains the gold standard for diagnosis of acute mesenteric ischemia (AMI), but is often unhelpful or too late due to non-specific clinical and radiological signs. This systematic review and meta-analysis aims to evaluate the diagnostic accuracy of the novel serological biomarkers intestinal fatty acid-binding protein (I-FABP), α-glutathione S-transferase (α-GST), d-lactate, ischemia modified albumin (IMA), and citrulline to detect AMI. A systematic search of electronic databases was performed to identify all published diagnostic accuracy studies on I-FABP, α-GST, d-lactate, IMA, and citrulline. Articles were selected based on pre-defined inclusion and exclusion criteria. Risk of bias and applicability were assessed. Two-by-two contingency tables were constructed to calculate accuracy standards. Summary estimates were computed using random-effects models. The search yielded 1925 papers, 21 were included in the final analysis. Pooled sensitivity and specificity for investigated biomarkers were: I-FABP (Uden); 79.0 (95% CI 66.5–88.5) and 91.3 (87.0–94.6), I-FABP (Osaka); 75.0 (67.9–81.2) and 79.2 (76.2–82.0), d-lactate; 71.7 (58.6–82.5) and 74.2 (69.0–79.0), α-GST; 67.8 (54.2–79.5) and 84.2 (75.3–90.9), IMA; 94.7 (74.0–99.9) and 86.4 (65.1–97.1), respectively. One study investigated accuracy standards for citrulline: sensitivity 39% and specificity 100%. The novel serological biomarkers I-FABP, α-GST, IMA, and citrulline may offer improved diagnostic accuracy of acute mesenteric ischemia; however, further research is required to specify threshold values and accuracy standards for different aetiological forms.