Background Older adults face several physical and psychological problems such as hearing loss, vision loss, and memory loss, which diminish the quality of their communication. Poor communication in turn affects their psychological wellbeing and induces substantial depression, anxiety, and stress. The family has an important role in the mental health of older adults. Objectives This study aimed to investigate the effect of a family-oriented communication skills training program on depression, anxiety, and stress in older adults. Patients and Methods For this randomized controlled clinical trial, we enrolled 64 older adults from two healthcare centers affiliated to the Isfahan University of Medical Sciences. The subjects were randomly allocated to an experimental group (n = 32) and a control group (n = 32). In the experimental group, older adults along with their primary caregiver participated in six sessions of communication skill education. The control group participated in two training sessions on nutrition and exercise. All participants answered the DASS21 questionnaire three times—at the start of the study, at the end of the sixth week, and a month after the last educational session of the experimental group. Data were analyzed using chi-square, Fisher’s exact and t tests and by repeated measures analysis of variance (ANOVA). Results In the experimental group, the mean depression score significantly reduced from 10.56 ± 3.34 before intervention to 7.46 ± 2.80 and 6.30 ± 2.75 after intervention and at follow-up, respectively; the mean anxiety score significantly reduced from 8.46 ± 1.88 before intervention to 5.83 ± 1.93 and 5.80 ± 2.12 after intervention and at follow-up, respectively; and the mean stress score significantly decreased from 11.40 ± 4.53 before intervention to 8.90 ± 3.81 and 8.43 ± 3.31 after intervention and at follow-up, respectively (P < 0.05 for all three domains). In contrast, the control group did not show any significant change in the mean depression, anxiety, and stress scores. Conclusions Family-oriented education on communication skills could reduce depression, anxiety, and stress in the elderly. Therefore, such programs should be adopted as a non-pharmacological and cost-effective method for reducing depression, anxiety, and stress in older adults.