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Rural communities in Kenya largely depend on plant resources for their livelihood. The utilization of these resources depends on the availability of plant resources and the level of knowledge of the residents. We conducted an ethnobotanical study in Tharaka-Nithi County in Kenya to determine the knowledge and utilization of various plant species by the local communities. The study was conducted in four major administrative regions from June 2018 to February 2019, involving interview schedules using semi-structured open-ended questionnaires and guided field collections with 48 informants. A total of 214 plant species distributed in 73 families and 169 genera with 616 Use Reports (URs) were documented. Fabaceae was the highest family cited by the informants (31 species) followed by Lamiaceae and Euphorbiaceae (each with 11 species). Trees (49%) and shrubs (32%) were the top life forms of the plants frequently utilized by the local residents. The general plant uses reported were medicinal, food, fodder, construction, fuel, pesticidal, religious, live fencing, and making crafts. Zanthoxylum gilletii, Prunus africana, and Solanum incanum were found to be highly valued by the local communities. Plant utilization as food and medicinal uses against snake-bite related problems had the highest Informant Consensus Factor (ICF). Only 29 (13.6%) of the species reported had their status assessed by the International Union for Conservation of Nature (IUCN). Conservation measures, alongside awareness creation in this region, are highly recommended for the species endemic to the region, highly depended on by the community, and those threatened according to IUCN standards.