Resistance training andDioscorea esculentaintake have a positive effect on muscle. Therefore, we aimed to determine whether 12-weekDioscorea esculentaintake combined with resistance exercise more effectively improves muscle quantity, quality, and cardiometabolic parameters in healthy middle-aged and older adults. This study is a double-blind trial with 66 volunteers (21 males/45 females; age 53 ± 5 years; body weight 61 ± 11 kg; BMI 24 ± 4 kg) who were randomly divided into four groups: sedentary-control with placebo (Sed and PL) or Dioscorea (Sed and Dio) and resistance training with placebo (RT and PL) or Dioscorea (RT and Dio). Resistance training sessions using elastic bands were performed 3 days/week for a 12-week period.Dioscorea esculentatablets were ingested at 2000 mg/day once per day. The RT and Dio group showed greater improvements in the femoris muscle’s thickness, echo intensity for the rectus femoris (index of muscle quality), and the five times sit-to-stand test compared to that of the Sed and PL group; the echo intensity in the RT and Dio group further improved compared to those in the Sed and Dio, and RT and PL groups (p< 0.05). The circulating levels of C1q (a potential biomarker of muscle fibrosis) in the RT and Dio group were significantly lower than those in the Sed and PL, and Sed and Dio groups (p< 0.05). ChronicDioscorea esculentaintake combined with low-intensity resistance exercise may more effectively improve muscle quantity and quality indices in healthy middle-aged and older adults.