The bioavailability of poorly soluble medications can be greatly improved by the use of nanocarriers (NCs) where; loading of drugs within NCs could improve the solubility, prevent degradation through enzymes of GIT and enhance the passage crosswise the gel mucus layer and absorption membrane. The surface chemistry of most of nanocarriers greatly affects all properties of NCs, specifically, food interaction, diffusion behavior through the gel mucus layer, and providence on the absorption membrane. Bioinert surfaces greatly decrease the interaction with GI fluids. Adhesive surfaces offer near connection with the mucosa of GIT and absorption. Moreover, charge-converting surfaces facilitate targeted drug release by shifting their zeta potential from negative to positive at absorption membranes. In addition, Active surfaces may cleave mucus glycoproteins. In this review, we deliberate the different types of surface modification of NCs and their impact on the efficacy of NCs as successful drug delivery systems. Moreover, the different techniques applied for NCs surface modifications through the use of diverse biomaterials to change their physicochemical characteristics, pharmacokinetic qualities, and pharmacological activity. Surface engineering may be utilized by undercoating the NCs either through the use of non-covalent bonds, covalent bonds, or special techniques.