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Purpose: This study investigated the effect of online home-based resistance exercise training on fitness, depression, stress, and well-being. A total of 67 individuals participated. Of them, 28 participants (13 men and 15 women, average age: 45.1 ± 12.2 years) performed the same exercise training online (n = 17), using Zoom, or in person (n = 11) in 2020 (Study 1). In addition, 39 participants (15 men and 24 women; average age: 47.6 ± 10.8 years) performed eight weeks of online home-based resistance exercise training in 2021 (Study 2). The participants performed low-load resistance exercises twice a week for eight weeks (16 sessions). Muscle strength, thigh muscle cross-sectional area, fitness parameters, blood pressure, mental health (Center for Epidemiologic Studies-Depression Scale—CES-D; and Kessler Psychological Distress scale—K6), and well-being (Well-Being Index—WHO-5) were measured pre-and post-resistance training. In Study 1, eight weeks of online home-based resistance training improved CES-D (p = 0.003), and a similar tendency was observed in resistance training (RT) with the in-person group (p = 0.06). There was a significant improvement in CES-D symptoms after the online home-based resistance training in Study 2 (p = 0.009). However, there were no significant changes in the WHO-5 and K6. Our results suggest that online low-load resistance training improves fitness parameters and curbs depressive status.