AimsTo examine the effects of a home‐based exergame training over 6 weeks on cardio‐metabolic and cognitive health, as well as training adherence, in physically inactive individuals.Materials and MethodsTwenty participants were equipped with an exergame system specifically designed for use at home. Each participant performed at least three weekly exercise sessions at ≥80% of their individual maximum heart rate, over 6 weeks. Exercise duration increased biweekly until 75 min of vigorous exercise were performed in Weeks 5 and 6. Maximum oxygen uptake (VO2max), cardio‐metabolic profiling, and neuro‐cognitive tests were performed at baseline and study end. Additionally, training adherence was assessed via training diaries.ResultsAfter 6 weeks of home‐based exergaming, VO2max increased significantly, while there was a significant decrease in heart rate (resting and maximum), blood pressure (systolic, diastolic and mean), and low‐density lipoprotein cholesterol. Dynamic balance and reaction time improved after 6 weeks of exergaming. Training adherence was 88.4%.ConclusionsHome‐based exergaming induced a clinically relevant increase in VO2max, a determinant of cardiovascular health, accompanied by further improvements in cardiovascular, metabolic and neuro‐cognitive parameters. Exergaming may, therefore, offer an innovative approach to increasing regular physical activity, improving metabolic risk profile, and preventing chronic diseases.