Cryptolepis sanguinolenta is an important medicinal plant used in the treatment of malaria in Ghana. Overharvesting, destruction of entire plant populations and poor seed viability have resulted in a substantial decrease in wild populations thereby threatening its long-term potential and survivability. In this study, fifteen polymorphic microsatellite loci were used to evaluate the genetic diversity and population structure of 179 C. sanguinolenta individuals among eight subpopulations in Ghana. The subpopulations were separated by a distance of 8.3 – 233.3 km. Our results indicated relatively high levels of genetic diversity (Ho= 0.41; He=0.61) and high gene flow (Nm=7.06), an indication of greater stability and adaptability within the ecosystem, limited genetic differentiation (mean FST=0.05; highest FST=0.1), which suggested insignificant differentiation among the subpopulations. The high levels of gene flow resulting from the wind-dispersed seeds might have contributed to the limited genetic differentiation among the subpopulations. The Bayesian cluster analysis revealed the presence of a population structure (K=2). A lack of isolation by distance (r=0.012; P=0.34) indicated an increase in the genetic similarity among the subpopulations as the geographic distance between them decreased. This study described the genetic diversity and population structure in the current C. sanguinolenta accessions and laid a foundation for future breeding efforts.