Antibiotics are among the most often used medications in human healthcare and agriculture. Overusing these substances can lead to complications such as increasing antibiotic resistance in bacteria or a toxic effect when administering large amounts. To solve these problems, new solutions in antibacterial therapy are needed. The use of natural products in medicine has been known for centuries. Some of them have antibacterial activity, hence the idea to combine their activity with commercial antibiotics to reduce the latter's use. This review presents collected information on natural compounds (terpenes, alkaloids, flavonoids, tannins, sulfoxides, and mycotoxins), of which various drug interactions have been observed. Many of the indicated compounds show synergistic or additive interactions with antibiotics, which suggests their potential for use in antibacterial therapy, reducing the toxicity of the antibiotics used and the risk of further development of bacterial resistance. Unfortunately, there are also compounds which interact antagonistically, potentially hindering the therapy of bacterial infection. Depending on its mechanism of action, each compound can behave differently in combination with different antibiotics and when acting against various bacterial strains.