: The available data on the relationship between dietary inflammatory index (DII) and serum lipids are controversial. This systematic review and meta-analysis aimed to investigate the relationship between DII and serum lipids, including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) in general populations. : PubMed, Web of Science, SCOPUS, and Cochrane electronic databases were systematically searched from inception to December 2019. Case-control, cohort or cross-sectional studies that evaluated the relationship between DII and serum lipids were included. The random-effects model was applied to evaluate the pooled weighted mean difference (WMD) and 95% confidence intervals (CI). : In total, twenty-four cross-sectional and one case-control studies with a total sample size of 129,759 were included in the meta-analysis. The pooled results showed that the highest category of DII was associated with 5.16 mg/dl increase in TC (Pooled WMD: 5.16; 95% CI: 0.58-9.73,  = 0.02) and 3.99 mg/dl increase in LDL-C (Pooled WMD: 3.99; 95% CI: 1.16-6.81,  = 0.006). However, no significant association between DII scores, HDL-C and TG was found. In subgroup analysis, the geographical region, gender, and dietary assessment methods were potent sources of heterogeneity. : This study showed that a higher level of DII was associated with higher levels of TC and LDL-C in apparently healthy populations. Since the included studies had observational designs, therefore, no conclusion of causality was possible. More studies with interventional designs are required to elucidate the causality of the observed association between DII and the risk of abnormal lipid profile.