Aim: Isotretinoin, the drug of choice for severe - nodulocystic acne, might be associated with an increase in insulin resistance. We aimed to investigate this association. Methods: We performed a systematic review and meta-analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement. A systematic search in PubMed/MEDLINE, SCOPUS and Cochrane databases was conducted until the 12th of January 2022 using the PICO tool (Patient, Intervention, Comparison, Outcome). Studies with a published full text in English regarding acne patients under isotretinoin were included. Insulin, glucose and adiponectin serum levels before and after isotretinoin treatment were recorded and insulin sensitivity was assessed using the homeostasis model assessment of insulin resistance (HOMA–IR). For Meta-analysis, the Review Manager (RevMan) 5.4.1 software was utilized. The quality assessment of the included studies was performed using the ROBINS-I tool. Results: Fifteen studies were included. The meta-analysis revealed a statistically significant increase in post-treatment adiponectin [SMD = 0.86; 95% confidence interval (CI) = 0.48 - 1.25, p-value <0.0001; I2 = 58%]. Subgroup analysis by study type revealed the same results [cohort studies pooled SMD = 1.2, 95% CI = 0.81 -1.61, p-value <0.00001; I2 = 8% and case-control studies pooled SMD = 0.53, 95% CI = 0.16 - 0.9, p-value=0.005; I2 = 27%)]. No statistically significant results were shown for insulin, glucose levels and HOMA-IR. Conclusion: Although isotretinoin exposure is not clearly associated with insulin resistance, it seems that it can increase serum adiponectin levels. Further research is needed to clarify this association.