This study examined the effects of khat chewing on oral gingival conditions by adopting a targeted process which combined physicochemical analyses of the teeth, histopathological examinations of the gums, and bioinformatics modeling. The physicochemical evaluation of teeth in khat consumers compared to non-consumers was carried out using specific analytical techniques; hence, the results of this initial investigation revealed significant erosion of the tooth enamel due to khat chewing, as well as an alteration of the essential chemical composition of the teeth. Additionally, the histopathological analyses complemented preliminary studies by showing severe inflammation of the gums and oral mucosa in khat users. The understanding of these studies was enriched by bioinformatics analysis, where modeling was carried out via computational methods. This analytical phase examined molecular docking mechanisms, including the interaction between cathinone, the main alkaloid of khat, and the protein receptors involved in the protection of gingival tissues against infections. In summary, this multidisciplinary research provided an in-depth view of the oral health issues related to khat chewing, combining experimental studies with bioinformatics perspectives.