Background/Objectives: The miswak, crafted from the Salvadora persica tree, is a traditional teeth-cleaning twig that has served as a natural substitute for toothbrushes and toothpaste across diverse regions for centuries. This study aimed to evaluate and compare the effectiveness of miswak and a conventional toothbrush in reducing dental plaque and gingivitis over a two-week period. Methods: This two-week randomized, single-blind (clinical investigator), two-parallel-arm clinical trial was conducted at Princess Nourah University College of Dentistry (PNUCD). Stratified random sampling identified sixty participants who were then randomly assigned to two study groups: the miswak group and the toothbrushing group. To facilitate data collection, a self-designed form was employed to document participants’ initials, assigned group, the Silness and Loe plaque index, and the Loe and Silness gingival index. The clinical examination, conducted by two blinded and trained examiners using a mouth mirror and explorer under natural light, aimed to assess the specified indices. The collected data were analyzed using IBM SPSS Statistics, Version 22. Results: Following the intervention, the miswak group exhibited no significant change in the plaque scores (p = 0.58) compared to the toothbrush group (p = 0.007). A notable rise in gingival score was observed within the miswak group (p < 0.001), whereas no significant change was noted within the toothbrush group (p = 0.52). Conclusions: Over a two-week period, miswak was successful in controlling dental plaque; however, gingival scores were higher, which could be attributed to the aggressive use of miswak. With proper training, the use of miswak has the potential to contribute positively to gingival health, particularly in regions where it is readily accessible and affordable.