γδT cells have emerged as a promising target in tumor therapy, prompting the development of novel strategies to activate these cells directly within the tumor microenvironment. In this study, we engineered uniformly sized spherical garlic-derived nanoparticles (GNPs) to stimulate tumor-infiltrating γδT cells. Through intratumoral injection of GNPs, we demonstrated their ability to directly activate γδT cells, leading to potent antitumor effects. This approach resulted in significant inhibition of various subcutaneous tumors in mice. Additionally, under computed tomography (CT) guidance, intratumoral injection of GNPs effectively suppressed the growth of orthotopic liver cancer in New Zealand white rabbits. Mechanistic studies revealed that GNPs robustly activated γδT cells, promoting an inflammatory microenvironment within tumors. Our approach of using garlic-derived nanoparticles offers the advantages of simplicity in preparation and high yield, presenting a promising avenue for tumor therapy with potential for clinical translation.