The purpose of this study was to investigate changes in the levels of myokines in post- menopausal obese females (PMOF) after regular aerobic and resistance training. A community-based, randomized controlled trial study of 41 PMOF from Buk-gu Community Center in Chuncheon, Gangwon-do, Republic of Korea, was conducted from November 2017 through October 2018. These participants were randomly assigned to an aerobic exercise group (n = 21) or a resistance exercise group (n = 20). The 12-week exercise program was conducted three days a week (Monday, Wednesday, and Friday). Body composition, physical fitness, and myokines were measured at baseline, 6 weeks, and 12 weeks. The two-way within-factor ANOVA revealed group × time interaction for body mass index (BMI, p < 0.05). In the resistance exercise group, muscle endurance (p < 0.001), power (p < 0.01), and agility (p < 0.001) improved significantly at 12 weeks compared to baseline and 6 weeks. In the aerobic exercise group, muscle strength (p < 0.05), flexibility (p < 0.05), muscle endurance (p < 0.001), and agility (p < 0.001) were greater at 12 weeks compared to baseline and 6 weeks. The levels of IL-6 (p < 0.001), IL-15 (p < 0.001), and BDNF (p < 0.001) were greater at 12 weeks compared to baseline and 6 weeks in both exercise groups. Aerobic exercise training and resistance exercise training changed the levels of myokines and improved body composition and physical fitness in PMOF. These findings provide preliminary evidence that PMOF need to exercise or perform physical activity to improve or maintain their levels of myokines and physical fitness.