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Metformin is the first-choice therapy to lower glycaemia and manage type 2 diabetes. Continuously emerging epidemiological data and experimental models are showing additional protective effects of metformin against a number of age-related diseases (ARDs), e.g., cardiovascular diseases and cancer. This evidence has prompted the design of a specific trial, i.e., the Targeting Aging with Metformin (TAME) trial, to test metformin as an anti-ageing molecule. However, a unifying or prevailing mechanism of action of metformin is still debated. Here, we summarize the epidemiological data linking metformin to ARD prevention. Then, we dissect the deeply studied mechanisms of action explaining its antihyperglycemic effect and the putative mechanisms supporting its anti-ageing properties, focusing on studies using clinically pertinent doses. We hypothesize that the molecular observations obtained in different models …