Epidemiological studies have shown a lower prevalence (AD) prevalence in men, although the underlying mechanisms are unclear. Microglia, the primary innate immune cells in the brain, release inflammatory cytokines and degrade aggregated amyloid β (Aβ) via autophagy, implying their role in sex-related AD susceptibility. In this study, we investigated the effect of testosterone, the major sex hormone in males, on Aβ-induced autophagy in microglia via GPRC6A, a non-genomic testosterone receptor. We confirmed that GPRC6A, but not the nuclear androgen receptor, is expressed in mouse microglial MG6 cells, indicating that GPRC6A mainly mediates testosterone signaling in MG6 cells. Testosterone suppressed ERK phosphorylation, activating autophagy and enhancing Aβ degradation. Extracellular Aβ was internalized by MG6 cells and co-localized with LC3, an autophagosome marker. Furthermore, co-stimulation with Aβ and testosterone amplified autophagic vacuoles, strengthening the link between testosterone and Aβ-induced autophagy. Genetic GPRC6A knockdown as well as GPRC6A inhibition counteracted this effect, implying testosterone-GPRC6A augmentation of Aβ-induced autophagy. This mechanism may contribute to the low susceptibility to AD in men.