BackgroundMalaria remains the leading cause of death in sub-Saharan Africa. Although recent developments such as malaria vaccine trials inspire optimism, the search for novel antimalarial drugs is urgently needed to control the mounting resistance ofPlasmodiumspecies to the available therapies. The present study was conducted to document ethnobotanical knowledge on the plants used to treat symptoms of malaria in Tororo district, a malaria-endemic region of Eastern Uganda.MethodsAn ethnobotanical study was carried out between February 2020 and September 2020 in 12 randomly selected villages of Tororo district. In total, 151 respondents (21 herbalists and 130 non-herbalists) were selected using multistage random sampling method. Their awareness of malaria, treatment-seeking behaviour and herbal treatment practices were obtained using semi-structured questionnaires and focus group discussions. Data were analysed using descriptive statistics, paired comparison, preference ranking and informant consensus factor.ResultsA total of 45 plant species belonging to 26 families and 44 genera were used in the preparation of herbal medicines for management of malaria and its symptoms. The most frequently mentioned plant species wereVernonia amygdalina,Chamaecrista nigricans,Aloe nobilis,Warburgia ugandensis,Abrus precatorius,Kedrostis foetidissima,Senna occidentalis,Azadirachta indicaandMangifera indica. Leaves (67.3%) were the most used plant part while maceration (56%) was the major method of herbal remedy preparation. Oral route was the predominant mode of administration with inconsistencies in the posology prescribed.ConclusionThis study showed that the identified medicinal plants in Tororo district, Uganda, are potential sources of new antimalarial drugs. This provides a basis for investigating the antimalarial efficacy, phytochemistry and toxicity of the unstudied species with high percentage use values to validate their use in the management of malaria.Supplementary InformationThe online version contains supplementary material available at 10.1186/s41182-023-00526-8.