Astrocytes are abundant cells in the central nervous system that regulate and support diverse neural functions. Activation of astrocytic G protein-coupled receptors (GPCRs) is a key mechanism through which astrocytes sense and regulate neural activities and behavior. It is well-established that the effects of astrocytic GPCRs are highly context-dependent and can vary with brain region, age, and other factors. However, it is not known if biological sex plays a significant role in how astrocytic receptors modulate behavior. Here, we tested whether astrocytic GPCRs regulate learning and memory in a sex-specific manner using four complementary in vivo manipulations. We first utilized CRISPR-Cas9 to inducibly knock down astrocytic metabotropic glutamate receptor 3 (mGluR3) in the hippocampus of adult mice. mGluR3 is a Gi/o-coupled receptor that serves as a central astrocytic sensor of glutamate, but its effects on brain function are not clear. We found that astrocyte-targeted knockdown of mGluR3 altered spatial memory in both sexes, but the effects differed in males and females. Specifically, mGluR3 knockdown impaired memory in females, but improved memory in males, suggesting that astrocytic mGluR3 regulates memory in a sexually dimorphic manner. To further test if changes in mGluR3 expression cause bidirectional effects on memory, we used Cre-dependent viral vectors to enhance astrocytic mGluR3 levels. Increasing mGluR3 improved memory in females but not males, indicating that the sex-specific effects of mGluR3 were bidirectional and not unique to the knockdown approach. We next tested if the sex-specific effects occurred with other types of astrocytic GPCRs. For these experiments, we used in vivo chemogenetic stimulation to selectively activate Gi/o- or Gs-coupled receptor signaling in hippocampal astrocytes during learning. In congruence with the effects of mGluR3 manipulation, activating astrocytic Gi/o- or Gs-coupled receptors modulated spatial memory in a bidirectional and sex-specific manner, suggesting that signaling by various astrocytic GPCRs is sufficient to induce sex-specific effects on memory. Additional methods were used to address potential mechanisms mediating these effects. Together, our findings reveal that astrocytic mGluR3 and other GPCRs regulate hippocampal function in a highly sex-specific manner, and alterations in astrocytic receptor signaling might contribute to sex differences in health and disease.