Prenatal hormone exposure has been suggested as a correlate of adult circulating estrogen and testosterone. If this observation is true, then prenatal hormone exposure may have an association with lipid homeostasis in adulthood. The study sought to investigate sexual dimorphism and the interactions between the putative marker of prenatal hormone exposure (2D : 4D) and sex on adult fasting plasma lipid variables. The study was cross-sectional from June to December 2021 at the University for Development Studies. The participants were between 18 and 30 years of age and consisted of 206 healthy persons ( female = 93 , male = 113 ). The right hand (2D : 4DR), the left hand (2D : 4DL), and the right-left 2D : 4D difference (Dr-l) were measured using computer-assisted analysis. Fasting venous blood samples were collected and analyzed for lipid variables including total cholesterol (TCHOL) and high-density lipoprotein cholesterol (HDL-C). There were no significant differences in the 2D : 4D ratio and lipid variables between males and females. However, after adjusting for age and BMI, the 2D : 4DR ( P = 0.014 ) and the 2D : 4DL ( P = 0.007 ) increased with increasing fasting plasma HDL-C on average. Moreover, there were significant interactions between sex and the 2D : 4DR ( P = 0.002 ) and also, the 2D : 4DL ( P = 0.005 ) on fasting plasma HDL-C. The relationship between HDL-C and the 2D : 4D ratio was positive in females but negative in males. The 2D : 4DR accounted for about 54.9% and 46.0% while the 2D : 4DL accounted for about 48.2% and 14.0% of the variabilities in fasting plasma HDL-C in females and males, respectively. Prenatal hormone exposure may partly account for the sexual dimorphism in adult lipid homeostasis.