Untreated caries and severe periodontal disease are the most frequently encountered reasons for the tooth loss in adult population all over the world, which leads to reduced quality of life. For many years, a plethora of studies revealed the fundamental role of the microorganisms in oral biofilm in the development of caries and periodontal destruction. The primary means of oral biofilm control are through mechanical action. Although toothbrushing removes biofilm from the buccal, oral, and occlusal surfaces, it does not reach efficiently into the interdental areas. Today, several interdental cleaning devices are available over the counter for individual needs. On the other hand, this variety may be confusing for the patients to choose the right device for themselves. Therefore, dental professionals are responsible to guide their patients according to their specific needs with an evidence-based approach. Since direct evidence for the relation of interdental cleaning and periodontal disease prevention is on research, there is still a need for randomized controlled studies on interdental cleaning to increase the strength of evidence. From this standpoint, the aim of this chapter is to evaluate the cleaning efficacy of different interdental cleaning devices regarding in vitro and in vivo aspects together with patient preference and acceptance.