Pharmaceutical excipients, commonly known as inactive ingredients, encompass any substance aside from the active ingredient that fulfills a distinct and vital role in a formulation. Their purpose is to enhance specific characteristics, whether associated with the performance of the formulation or aspects related to patient comfort, safety, and acceptability. Because of the limited toxicity studies provided, and the several allergic and toxic side effects that have been reported throughout the years, it is not trivial for the regulatory agencies to approve inactive ingredients for human use. In general, excipients are approved within good manufacturing practices (GMPs) when they undergo analysis of the formulation as a whole, not the standalone substance. However, there is a lack of updated information regarding this subject, given that only the American Food and Drug Administration (FDA) provides a complete list describing the inactive ingredients that are currently approved in drug products for human use. Here, we aimed to provide an overview of key excipients approved by the FDA for ophthalmic use in humans, focusing on their functional roles in ophthalmic formulations, particularly eye drops, and the regulatory requirements involved in these ingredients approval.