This study explored the effects of a comprehensive health-care program (CHCP) on blood pressure, blood glucose, body composition, and depression in older adults living alone. We used a quasi-experimental, two-group, pretest–posttest design. The CHCP consisted of open lectures, health counseling, exercise classes, nutrition counseling, and self-help group meetings at a local senior welfare center. Fifty-eight subjects participated in this study, with thirty subjects in the experimental group and twenty-eight subjects in the control group. Data were analyzed by using the descriptive statistics, χ2-test, and t-test. Comparisons of the pretest and posttest systolic blood pressure (t = −2.530, p < 0.016) and blood glucose (t = 3.089, p < 0.004) between the experimental and control groups showed significant differences. In both the experimental (t = 3.949, p < 0.001) and control groups (t = 3.816, p < 0.002), depression symptoms showed a significant decrease posttest, compared with pretest. Our findings infer that older adults require physical and psychosocial health care and that more efforts must be made to improve the general health and well-being of this population group.