Abnormal calcium homeostasis has been associated with impaired glucose metabolism. However, the epidemiological evidence is controversial. We aimed to assess the association between circulating calcium levels and the risk of type 2 diabetes mellitus (T2DM) or abnormal glucose homeostasis through conducting a systematic review and meta-analysis. Eligible studies were identified by searching electronic database (PubMed, Embase, and Google Scholar) and related references with de novo results from primary studies up to December 2018. A random-effects meta-analysis was performed to estimate the weighted relative risks (RRs) and 95% confidence intervals (CIs) for the associations. The search yielded 20 eligible publications with 8 cohort studies identified for the meta-analysis, which included a total of 89,165 participants. Comparing the highest to the lowest category of albumin-adjusted serum calcium, the pooled RR was 1.14 (95% CI, 1.05, 1.24) for T2DM (n=51,489). Similarly, serum total calcium was associated with incident T2DM (RR, 1.25; 95% CI, 1.10, 1.42) (n=64,502). Additionally, the adjusted RR for 1 mg/dL increments in albumin-adjusted serum calcium or serum total calcium levels was 1.16 (95% CI, 1.07, 1.27) and 1.19 (95% CI, 1.11, 1.28), respectively. The observed associations remained with the inclusion of a cohort study with ionized calcium as the exposure. However, data pooled from neither case-control (n=4) nor cross-sectional (n=8) studies manifested a significant correlation between circulating calcium and glucose homeostasis. In conclusion, accumulated data from the cohort studies suggest that higher circulating calcium levels are associated with an augmented risk of T2DM.