Integrase Strand Transfer Inhibitors (INSTIs) are a type of antiretroviral medication used primarily for the treatment of HIV/AIDS. They work by inhibiting the activity of the HIV integrase enzyme, which is required for the virus to replicate within human cells. HIV, a retrovirus, employs integrase to integrate its viral DNA into the host cell's DNA, a step required for reproduction. INSTIs function by attaching to the integrase enzyme and preventing viral DNA from being integrated into the host cell's genetic material. This reduces the virus's capacity to cause a lasting infection and generate new viral particles. INSTIs represented a substantial advancement in HIV treatment due to their powerful antiviral action, relatively acceptable side effect profile, and high barrier to resistance development. Raltegravir, Elvitegravir, Dolutegravir, and Bictegravir are some of the most regularly utilized INSTIs. These drugs are frequently used as part of combination therapy known as highly active antiretroviral therapy (HAART) or antiretroviral therapy (ART). Combining INSTIs with other antiretroviral medicines, such as nucleoside reverse transcriptase inhibitors (NRTIs) or protease inhibitors, is a common strategy for efficiently suppressing viral replication and lowering viral load in HIV-infected persons. INSTIs are generally well accepted, but like all medications, they can have negative effects. Common adverse effects include headaches, nausea, diarrhea, and exhaustion, which are usually minor and brief. In other situations, INSTIs can cause more serious side effects, such as allergic reactions or abnormalities in liver enzymes. INSTIs are renowned for their strong genetic resistance barrier. INSTI resistance is less common than resistance to other types of antiretroviral medicines. However, like with all antiretroviral drugs, adherence to the recommended treatment plan is critical to preventing the establishment of drug-resistant HIV strains. Continued research aims to increase the effectiveness and tolerability of INSTIs, as well as to investigate new formulations and combination medicines that can improve HIV treatment outcomes. The development of these inhibitors has made a substantial contribution to HIV/AIDS management, providing for better disease control and a higher quality of life for those living with HIV.