Introduction <p>Gender medicine focuses on disease differences between females and males regarding symptoms, treatment, prognosis, psychosocial effects and prevention. Acromegaly is a rare endocrine disorder caused by excessive growth hormone (GH) production, in the vast majority of cases due to the presence of a GH-secreting pituitary adenoma. Chronic GH elevation leads to increased insulin-like growth factor-1 (IGF-1), resulting in tissue overgrowth and a number of comorbidities. Among these, patients with acromegaly can experience various issues of the cardiovascular and metabolic system, including glucose metabolism unbalance, diabetes mellitus, arterial hypertension and cardiomyopathy.</p> Aim and methods <p>This narrative review discusses the impact of gender differences on glycometabolic and cardiovascular comorbidities in patients with acromegaly. We performed a detailed literature search, gathering scientific articles on this topic, including original research studies, case reports, reviews, systematic reviews, meta-analyses, guidelines, and consensus papers published in English from 1989 to early 2025.</p> Results <p>A diagnostic delay between females and males is reported, together with a gender-related impact of the disease on body composition, lipid and glucose metabolism; gender differences in the development and progression of acromegaly cardiomyopathy are also described. In detail, females with acromegaly exhibit greater insulin resistance, increased adiposity, and higher risk of developing overt diabetes mellitus compared to males, along with milder cardiac abnormalities, despite experiencing higher cardiovascular mortality.</p> Conclusion <p>Gender differences in metabolic and cardiovascular comorbidities of acromegaly need to be considered. Future studies should clarify the biological bases of these differences, to optimize treatment protocols and monitoring for our patients.</p>