The optical properties of quantum dots (QD) make them excellent candidates for bioimaging, biosensing, and therapeutic applications. However, conventional QDs are comprised of heavy metals (e.g., cadmium) that pose toxicity challenges in biological systems. Synthesising QDs without heavy metals or introducing thick surface coatings, e.g., by encapsulation in micelles, can reduce toxicity. Here, we examined the toxicity of micelle encapsulated tetrapod-shaped Mn-doped ZnSe QDs, comparing them to 3-mercaptopropionic acid (MPA)-capped Mn-doped ZnSe QDs prepared by ligand exchange and commercial CdSe/ZnS QD systems that were either capped with MPA or encapsulated in micelles. HepG2 cell treatment with MPA-coated CdSe/ZnS QDs resulted in a dose-dependent reduction of viability (MTT assay, treatment at 0–25 μg/mL). Surprisingly, no reactive oxygen species (ROS) or apoptotic signaling was observed, despite evidence of apoptotic behavior in flow cytometry. CdSe/ZnS QD micelles showed minimal toxicity at doses up to 25 μg/mL, suggesting that thicker protective polymer layers reduce cytotoxicity. Despite their shape, neither MPA- nor micelle-coated Mn-doped ZnSe QDs displayed a statistically significant toxicity response over the doses investigated, suggesting these materials as good candidates for bioimaging applications.