Tramadol is often recommended by healthcare professionals to help manage pain levels in patients suffering from various illnesses. Several studies have confirmed a connection between tramadol use and increased oxygen-free radicals, as well as activation of apoptosis and autophagy signaling pathways. These factors could damage the neuronal activities and ultimately cause brain damage. the abuse of tramadol is becoming more prevalent, with a noticeable rise in incidents involving poisoning and even fatalities associated with this particular drug. there has been a lack of review articles specifically examining the impacts of tramadol on neurodegeneration by focusing the oxidative stress, autophagy, and apoptosis signaling pathways. The objective of this current research was to examine the most recent animal experiments regarding the impact of prolonged tramadol exposure on causing neurotoxicity via oxidative stress, autophagy, and apoptosis pathways. Specially, provides insights into molecular and cellular mechanisms. This review indicates the increase of oxidative stress activity, apoptosis, and neuroinflammation and the decrease of antioxidant enzymes and neurotrophic factors following the chronic use of tramadol in different brain regions in animals. This implies that the damage caused to the nerve cells can be regarded as the primary concern when considering the chronic administration of this medication. Future research should prioritize well-designed clinical trials to assess the safety and effectiveness of tramadol in humans.