Background: This quasi-experimental study aimed to examine the effect of the modified transtheoretical theory of stress and coping (TTSC) program on the knowledge, burden, and quality of life of dementia caregivers. Methods: The participants comprised 60 caregivers (30 participants in each group) selected via purposive sampling, and the study was conducted between October 2018 and September 2019 in a semi-urban area of central Thailand. The experimental group received an 8-week program, while the comparison group received routine care. A self-administered questionnaire was used to collect data. To analyze the intervention's effectiveness, repeat measure ANOVA and Mann-Whitney, Friedman, and Dunn's tests were performed. Results: At the end of the program and again three months after the end of the program, the knowledge and quality of life scores for the experimental group were significantly higher (p < 0.05 and p < 0.05, respectively) than for the control group. The burden score decreased in the experimental group and increased in the control group in week 8 (p < 0.05). There was no statistically significant difference between the groups, as demonstrated by ANOVA (F[1.58] = 2.394; p = 0.127). Conclusions: Our findings show that this program had a positive effect on the caregivers' knowledge and quality of life. However, the program did not affect the caregivers' burden.