Nonalcoholic fatty liver disease (NAFLD) is one of the major global health issues, strongly correlated with metabolic disorder, insulin resistance, obesity and oxidative stress.  It is characterized by an excessive accumulation of liver fat, inflammation and dysfunction of the hepatocytes. NAFLD predisposes to cirrhosis, cardiovascular disease, and hepatocellular carcinoma in susceptible individuals. Although the specific signals remain poorly understood, NAFLD pathogenesis can involve the behavior of different types of hepatic cells and several extra-hepatic signals. The difficulty of NAFLD has been a big impediment to advancement and effective therapies with appropriate indicators. NAFLD's alternative medicines with medicinal herbs become the most useful solution today because of their minimum side effects. Phyllanthus niruri (P. niruri) is an herbal medicine that contains various bioactive phytochemicals with hypolipidemic, antioxidant, detoxifying, antimutagenic, anti-inflammatory and antiviral activities. The reduction of fatty acids and decreased insulin resistance (IR) is expected after P. niruri administration, which helps in the prevention of NAFLD. In this review, we describe recent clinical and diagnostic methods examining the diagnosis, development, and effects of NAFLD; comparing the attributes of the genetic and dietary animal models of NAFLD; and highlighting the potential hepatoprotective function of P. niruri, plus its therapeutic role in the prevention of NAFLD.