Purpose: The life satisfaction of Korean adolescents tends to decrease beginning in middle school, and this decrease has a negative effect on life satisfaction in adulthood. Gender and perceptions of parental neglect are important variables influencing the life satisfaction of adolescents in Korea. This study examined the longitudinal mediating effects of perceived parental neglect on the life satisfaction of male and female Korean adolescents to assess changes to the relationships between key variables over time. Methods: The present study analyzed data from 2,215 adolescents from the Korean Children and Youth Panel Survey's fourth-year elementary school panel spanning their first year of middle school (2013) to the first year of high school (2016). A latent growth model was applied to Korean national data. Results: The perceived parental neglect and life satisfaction intercepts differed by gender, and the intercept of perceived parental neglect influenced the life satisfaction intercept. The slope of perceived parental neglect, but not the life satisfaction slope, differed by gender, and the slope of perceived parental neglect influenced the life satisfaction slope. The Sobel method showed that the intercept of perceived parental neglect mediated gender differences in the life satisfaction intercept, and the slope of perceived parental neglect significantly influenced the gender difference in the life satisfaction slope. Conclusion: Efforts to improve adolescent life satisfaction should be differentiated by gender regarding perceptions of parental neglect.