Paracetamol is the most used non-opioid analgesic in the world, and it is used to relieve mild to moderate pain. On the other hand, phytotherapy is the use of plants or herbal supplements with known pharmacological effects. It is common for patients to use phytotherapy in conjunction with conventional drugs. Drug interactions are pharmacological responses in which the effects of one or more medicinal products are altered by their joint administration. The objective of this study is to evaluate the interaction between phytotherapics and paracetamol when administered together. Methods: The protocol of this review was registered in the PROSPERO/ CRD42018100106 international database for systematic reviews. The research question for this study was: Is there an interaction between phytotherapics and paracetamol when given together? Six databases were screened: PubMed (Medline); Lilacs; Ibecs; BBO; Scielo; and Google Scholar, using the search strategy developed for PubMed (Medline). Results and Conclusion: Use of garlic, saffron, eucalyptus, Devil's Claw, pomegranate, ginger, celery, ginkgo, Kava-kava, salsa, and salgueiro could interfere with the effects of paracetamol, producing, for example, greater bleeding and liver failure, and putting the health of the patient at risk. However, the use of phytotherapy in combination with paracetamol has also shown benefits. For example, acetaminophen-induced oxidative damage can be alleviated by the use of some plants due to their antioxidant potential. Other plants have nephroprotective action and can inhibit the progression of hepatic injury. To promote the responsible use of phytotherapy, when used with conventional drugs, we must know the effects of this interaction.