In the present study, we aimed to evaluate the anticancer effect of zinc oxide nanoparticles (ZnO-NPs) synthesized from Turbinaria conoides against a murine model of Dalton's lymphoma ascites (DLA). Nanoparticles were synthesized from the hydroethanolic extract of T. conoides (HETC). An ultraviolet-visible spectrophotometric analysis was performed to confirm the formation of ZnO-NPs. Size, morphology, and elemental composition of ZnO-NPs were also analyzed using scanning electron microscopy-energy dispersive X-ray diffraction (SEM-EDX). Healthy Swiss albino mice were intraperitoneally induced with DLA cells and treated with ZnO-NPs and HETC at a dose of 50 μg/kg (p.o.). The effects of ZnO-NPs and HETC on body weight, tumor volume, hematological profile, and liver biochemical parameters were studied. The results of in vivo studies revealed that the treatment with ZnO-NPs and HETC decreased the tumor volume, thereby increasing the lifespan of DLA-bearing mice. The treatment also restored the alterations in hematological profile, antioxidant status, and activities of liver marker enzymes. These histopathological results provided the evidence for the protective effect of ZnO-NPs and HETC on DLA-induced mice. Thus, we conclude that ZnO-NPs possess more significant anticancer and antioxidant activities in DLA-bearing mice than HETC.