Background Globally, 80% people use plant-derived products for treating or preventing diseases. One prevalent perception about medicinal plants is that they are safe and devoid of adverse effects. However, approximately 1,50,000 plants contain toxic substances. Objective The present review focuses on medicinal plant extracts/fractions toxicity assessments made in preclinical models by oral route. Methods Detail studies were searched from databases including PubMed and Google Scholar. A manual reference screening of the selected studies was done to identify relevant articles, with no language restriction being imposed at the time of searching. Results The studies included were performed in rodents, and the test substances were administered orally. Our search revealed 33 widely used plants or products with significant toxicity, and phytochemicals from these plants have been summarized. Through a systematic review, we identified a plethora of medicinal plant extracts reporting safety and toxicity concerns. Conclusion In the future, preclinical toxicokinetic studies of herbs and the determination of their no-observed-adverse-effect levels are required for a complete safety assessment. Finally, the interaction of herbs with commonly used/over-the-counter drugs in terms of the latter's metabolic profile should be undertaken.