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Purpose: This study examined the effect of the smartphone-based intervention program using laughter therapy on psychological and biological factors of the middle aged and older adults living alone.Methods: Data collection was conducted by a structured questionnaire about depression, loneliness, life satisfaction, and biological factors including general characteristics for the subjects residing in Cheonan, Korea. The collected data were analyzed by <i>x</i>² test, t-test using SPSS/WIN ver. 26.0. There were 28 experimental and 31 control subjects.Results: The experimental group received laughter therapy for 4 weeks along with usual care. The control group received usual care only. After 4 weeks, there was a statistically significant difference in depression (t=-3.28, <i>p</i>=.002), life satisfaction (t=-2.89, <i>p</i>=.006), and Immunoglobulin M (IgM) (t=-2.36, <i>p</i>=.021) between the two groups.Conclusion: This study presents growing evidence for the diverse applications and benefits of laughter and humor. When using laughter as a complementary method to enhance health, it will be more effective to tailor the program to the specific needs of the individual.