Urolithiasis is a disease characterized by the formation of stones, which are crystalline accretions that form in the urinary tract from minerals dissolved in the urine. Moreover, it is considered to be a complex and multifactorial disease, requiring treatment. Unfortunately, current treatments are insufficient or may induce several side effects. In fact, medicinal plants are among the anti-litholytic treatments that are strongly recommended by many studies. Indeed, these natural resources contain bioactive molecules of different natures, such as flavonoids, terpenoids, alkaloids, and phenolic acids, which have recently demonstrated very important anti-litholytic effects. The molecular mechanisms involved are multiple and variable, and can reach cellular and molecular levels. In this review, we have discussed in depth the work that has studied the bioactive molecules of medicinal plants and their major potential against urolithiasis. Scientific databases, including Web of Science, PubMed, and Google Scholar, were searched from their inception until April 2021.The cellular and molecular mechanisms are presented and discussed. Some mechanisms of action related to these bioactive compounds are highlighted. This review could provide a scientific starting point for further studies on urolithiasis and natural bioactive compounds, especially flavonoids.