Background. Infections by microbes (viruses, bacteria, and fungi) and parasites can cause serious diseases in both humans and animals. Heavy use of antimicrobials has created selective pressure and caused resistance to currently available antibiotics, hence the need for finding new and better antibiotics. Natural products, especially from plants, are known for their medicinal properties, including antimicrobial and anthelmintic activities. Geoclimatic variation, together with diversity in ethnomedicinal traditions, has made the Himalayas of Nepal an invaluable repository of traditional medicinal plants. We studied antiviral, antibacterial, antifungal, and anthelmintic activities of medicinal plants, selected based upon ethnobotanical evidence. Methods. Ethanolic and methanolic extracts were tested (1) on a panel of microbes: two Gram-positive bacteria (Staphylococcus aureus and Listeria innocua), four Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa, Salmonella enterica, and Shigella sonnei), and one fungal species: Candida albicans; (2) against three different viruses: yellow fever, chikungunya, and enterovirus; and (3) on the nematode Caenorhabditis elegans. Also, cytotoxicity was assessed on human hepatoma (Huh), rhabdosarcoma (RD), and Vero (VC) cell lines. Results. Of 18 plants studied, Ampelocissus tomentosa and Aleuritopteris anceps inhibited S. aureus (MIC 35 μg/mL and 649 μg/mL, respectively) and Pseudomonas aeruginosa (MIC 15 μg/mL and 38 μg/mL, respectively). Rhododendron arboreum and Adhatoda vasica inhibited S. enterica (MIC 285 μg/mL and 326 μg/mL, respectively). Kalanchoe pinnata, Ampelocissus tomentosa, and Paris polyphylla were active against chikungunya virus, and Clerodendrum serratum was active against yellow fever virus (EC50 15.9 μg/mL); Terminalia chebula was active against enterovirus (EC50 10.6 μg/mL). Ampelocissus tomentosa, Boenninghausenia albiflora, Dichrocephala integrifolia, and Kalanchoe pinnata significantly reduced C. elegans motility, comparable to levamisole. Conclusions. In countries like Nepal, with a high burden of infectious and parasitic diseases, and a current health system unable to combat the burden of diseases, evaluation of local plants as a treatment or potential source of drugs can help expand treatment options. Screening plants against a broad range of pathogens (bacteria, viruses, fungi, and parasites) will support bioprospecting in Nepal, which may eventually lead to new drug development.