When creating pharmaceutical dosage forms, the selection of excipients plays a significant role in the preformulation and formulation research. Excipients physical, mechanical, and chemical characteristics have a big impact on the final product and other formulation parameters like disintegration, dissolution, and shelf life. As a result, numerous studies have been carried out to assess how drug-excipient interactions affect the formulation as a whole. The information on excipients physical and chemical instability and compatibility with the active pharmaceutical component in solid oral dosage forms during various drug manufacturing procedures is reviewed in this article. The impact of these interactions on the drug formulation process has been discussed in detail. Examples of various excipients used in solid oral dosage forms have been included to elaborate on different drug-excipient interactions.