Diabetes mellitus (DM) and premenstrual syndrome (PMS) are global health challenges. Both disorders are often linked to a range of physical and psychological symptoms that significantly impact the quality of life of many women. Yet, the exact relation between DM and PMS is not clear, and the management of both conditions poses a considerable challenge. In this review, we aimed to investigate the interplay between DM, anti-diabetic drugs, and the different theories and symptoms of PMS. Female sex hormones are implicated in the pathophysiology of PMS and can also impair blood glucose control. In addition, patients with diabetes face a higher susceptibility to anxiety and depression disorders, with a significant number of patients experiencing symptoms such as fatigue and difficulty concentrating, which are reported in patients with PMS as well. Complications related to diabetic medications, such as hypoglycemia (with sulfonylurea) and fluid retention (with thiazolidinediones) may also mediate PMS-like symptoms. DM can, in addition, disturb the normal gut microbiota (GM), with a consequent loss of beneficial GM metabolites that guard against PMS, particularly the short-chain fatty acids and serotonin. Among the several available anti-diabetic drugs, those (1) with an anti-inflammatory potential, (2) that can preserve the beneficial GM, and (3) possessing a lower risk for hypoglycemia, might have a favorable outcome in PMS women. Yet, well-designed clinical trials are needed to investigate the anti-diabetic drug(s) of choice for patients with diabetes and PMS.