Background It is thought that inflammation significantly contributes to the development of bipolar disorder (BD), and recent findings indicate a connection between cystatin C and immune-related inflammation. In this study, we investigated serum cystatin C levels in patients with BD and explored the relationship between cystatin C and inflammatory markers.Methods The study involved 3,647 individuals diagnosed with BD, comprising 2,431 with BD-manic (BD-M) and 1,216 with BD-depression (BD-D), alongside 3,500 healthy controls. The analysis covered cystatin C levels and inflammatory biomarkers obtained from complete blood counts across the various groups. The Spearman correlation test was used to examine the relationship between cystatin C and inflammatory markers. Logistic regression and ROC curve analyses assessed the predictive value of these markers for disease occurrence.Results Serum cystatin C levels were significantly elevated in BD patients, particularly those in manic episodes, compared to the healthy control group, with distinct correlation patterns with inflammatory biomarkers observed among the groups. Serum Cystatin C levels independently and positively indicated disease occurrence, showing improved diagnostic effectiveness when combined with inflammatory ratios.Conclusion Our research indicates that cystatin C could be involved in the pathophysiological mechanisms of BD by affecting pro-inflammatory processes. Additionally, it should be emphasized that cystatin C showed considerable predictive capacity in diagnosing BD, especially when used alongside various inflammatory markers.Limitations The cross-sectional study is limited to demonstrating associations rather than establishing causality. A thorough examination of sociodemographic factors and the severity of the disease could not be conducted.