Poly(3-hydroxybutyrate) (PHB) and poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) are biopolyesters reported to provide favorable microenvironments for cell culture and possess potential for tissue engineering applications. Both biopolymers have been investigated for applications in a variety of medical scenarios, including nerve and bone repair. This study investigated the influence these biomaterials exerted on cell cycle progression of olfactory ensheathing cells (OECs) and mesenchymal stem cells (MSCs) commonly used in the engineering of nerve and bone tissues. Cell cycle regulation is important for cell survival; analysis revealed that the biomaterials induced significant cell cycle progression in both MSCs and OECs. Significantly higher percentages of cells were cycled at synthesis (S) phase of the cycle on PHBV films compared to PHB, with MSCs more susceptible than OECs. Furthermore, detection of early stages of apoptotic activation showed significant differences in the two cell populations exhibiting necrosis and apoptosis when cultivated on the biomaterials. OECs compromised on PHB (5.6%) and PHBV (2.5%) compared to MSCs with 12.6% on PHB and 17% on PHBV. Significant differences in crystallinity and surface rugosity were determined between films of the two biomaterials, 88% and 1.12 μm for PHB and 76% and 0.72 μm for PHBV. While changes in surface properties may have influenced cell adhesion, the work presented here suggests that application of these biomaterials in tissue engineering are specific to cell type and requires a detailed investigation at the cell-material interface.