An increased number antibiotic-resistant bacteria have emerged with the rise in antibiotic use worldwide. As such, there has been a growing interest in investigating novel antibiotics against antibiotic-resistant bacteria. Due to the extensive history of using plants for medicinal purposes, scientists and medical professionals have turned to plants as potential alternatives to common antibiotic treatments. Unlike other antibiotics in use, plant-based antibiotics have the innate ability to eliminate a broad spectrum of microorganisms through phytochemical defenses, including compounds such as alkaloids, organosulfur compounds, phenols, coumarins, and terpenes. In recent years, these antimicrobial compounds have been refined through extraction methods and tested against antibiotic-resistant strains of Gram-negative and Gram-positive bacteria. The results of the experiments demonstrated that plant extracts successfully inhibited bacteria independently or in combination with other antimicrobial products. In this review, we examine the use of plant-based antibiotics for their utilization against antibiotic-resistant bacterial infections. In addition, we examine recent clinical trials utilizing phytochemicals for the treatment of several microbial infections.