Kalaharia uncinata (Schinz) Moldenke (Lamiaceae), is a tropical erect bushy shrub or subshrub, endemic of Southern Africa, and widely used in the pharmacopoeia against upper respiratory tract infections. A previously conducted ethnobotanical survey revealed that it is believed to contain bioactive substances. However, no relevant phytochemical information was available. This study aimed to perform a phytochemical characterization of K. uncinata and to discuss the potential bioactivity of the identified phytochemical constituents based on documented data. Ultra‐performance liquid chromatography with electrospray ionization quadrupole time‐of‐flight mass spectrometry (UPLC‐ESI‐QTOF‐MS) was used for profiling and identification of the main phytochemical constituents from leaf extracts (MeOH 90%, dichloromethane, EtOAc, n‐BuOH, n‐hexane and residue) of K.uncinata. Twenty‐four constituents, representing mainly flavonoids (14), followed by phenylethanoid glycosides (7), phenolic acids (2), and an iridoid glycoside (1) were tentatively identified. K. uncinata contains interesting compounds. Most of the identified compounds are documented to have antiviral and anti‐inflammatory properties, which could possibly be the rationale behind the use of K. uncinata against upper respiratory tract infection. Further studies would be required to elucidate the exact structures of the tentatively identified compounds, as well as to evaluate their efficacy against upper respiratory tract infections and to evaluate their effectiveness.