Background: Previous studies have identified the relationships between parental parenting style, personality, and mental health. However, the interactive influences between mother’s and father’s parenting styles on personality have been examined less often. To fill the gaps, the first aim of this study was to build the relationships between parental parenting style differences (PDs) and five-factor personality dimensions. The second aim was to test the mediating effect of five-factor personality dimensions on the relationships between parental parenting style differences and mental health. Methods: This is a cross-sectional study conducted among medical university students, and 2583 valid participants were analyzed. Mental health was measured by the Kessler-10 scale. The Chinese Big Five Personality Inventory brief version (CBF-PI-B) was used to access five-factor personality dimensions. PD was calculated by the short form of Egna Minnen av Barndoms Uppfostran. Linear regressions were conducted to analyze the associations between PD and five-factor personality dimensions. The SPSS macros program (PROCESS v3.3) was performed to test the mediating effect of five-factor personality dimensions on the associations between PD and mental health. Results: Linear regressions found that worse mental health was positively associated with PD (β = 0.15, p < 0.001), higher neuroticism (β = 0.61, p < 0.001), lower conscientiousness (β = −0.11, p < 0.001), lower agreeableness (β = −0.10, p < 0.01), and lower openness (β = −0.05, p < 0.05). The results also supported that PD was positively associated with lower conscientiousness (β = −0.15, p < 0.01), lower agreeableness (β = −0.09, p < 0.001), lower openness (β = −0.15, p < 0.001), and lower extraversion (β = −0.08, p < 0.001), respectively. The mediating effect of agreeableness or openness was supported for the relationships between PD and mental health. Conclusion: These findings remind us of the importance of consistent parenting styles between mother and father, and they also can be translated into practices to improve mental health among medical university students.