Infectious diseases are major threats to humankind and are main reasons for mass mortality. As a survival mechanism microbes continuously evolve and change their genetic make up to gain resistance against the drugs which they come in contact. Hence, there is a growing interest in identifying alternative and safe medicines to overcome microbial drug resistance. The use of medicinal plants against various diseases has been mentioned in Ayurveda and the knowledge of usage has been transferred over the generation through oral tradition. The active principles behind the medicinal property of plants were not studied in traditional medicine. With the advent of modern tools, the active principals behind the broad-spectrum anti-microbial activity of medicinal plants were attributed to the presence of variety of bioactive compounds. The formulations or the extracts containing mixture of bioactive compounds are considered as GRAS and each one has various therapeutic applications. The bioactive compounds are secondary metabolites which play a pivotal role in solving the issues of microbial drug resistance and other ailments. In this review five medicinal crops (Aloe vera, Cynodon, Datura, Euphorbia, and Ocimum) were selected to review the significance of these crops in alternative medicine. The cause and mechanisms of microbial resistance to commonly used drugs are discussed. The historical aspects, the bioactive compounds, the broad-spectrum antimicrobial property and market potential of these crops are reviewed in the context of alternative medicine.