Periprosthetic joint infection (PJI) is one of the most intractable orthopedic diseases, partly because of the difficulty in differentiating septic from aseptic conditions. We aimed to evaluate and consolidate the diagnostic accuracy of the quantitative assessment of serum albumin (Alb), globulin (Glb), and albumin–globulin ratio (AGR), alone or in combination with the inflammatory marker, C-reactive protein (CRP), for PJI. We searched the PubMed, CINAHL, and Cochrane Library databases for studies that quantitatively measured Alb, Glb, or AGR for the diagnosis of PJI up until the 30 April 2023. A total of 2339 patients were included from 10 studies, including 845 patients with a definitive diagnosis of PJI and 1494 with non-PJI. The pooled sensitivity, specificity, and area under the curve (AUC) in the summary receiver-operating characteristic curve were as follows: 0.625, 0.732, and 0.715 for Alb; 0.815, 0.857, and 0.887 for Glb; 0.753, 0.757, and 0.875 for AGR; 0.788, 0.837, and 0.876 for CRP; 0.879, 0.890, and 0.917 for the CRP–Alb ratio; and 0.845, 0.855, and 0.908 for the CRP–AGR ratio. Serum Alb, Glb, and AGR levels are feasible and accurate diagnostic markers for PJI, and the combination of these markers with CRP levels may potentially improve preoperative serum diagnostic accuracy. Future prospective studies are required to verify these findings because of the small numbers of included studies.