The co-abuse of methamphetamine (METH) and human immunodeficiency virus (HIV) infection is a widespread public health issue nowadays. METH and HIV-1 Tat protein can independently and synergistically exert neurotoxicity on nerve cells. The damage of nerve cells is one of the causes of nervous system injury, and it is an important factor promoting the occurrence and development of HIV-associated neurocognitive disorders (HAND). Among them, microglia, as immune cells in the central nervous system (CNS), play a key role in the development, balance and innate immunity of the CNS under physiological conditions. Under pathological conditions such as toxic damage, microglia can undergo significant pathological changes, thereby promoting the occurrence and development of neurological dysfunction. This article reviews the research progress in recent years on the neurotoxicity of METH and HIV-1 Tat protein on microglia independently and synergistically, and evaluates this neurotoxicity from the perspective of microglial pathological changes, aiming to provide reference basis for the treatment and intervention targets of this special population with HAND after drug abuse combined with HIV infection.