Hydrogel has been an attractive biomaterial for tissue engineering, drug delivery, wound healing, and contact lens materials, due to its outstanding properties, including high water content, transparency, biocompatibility, tissue mechanical matching, and low toxicity. As hydrogel commonly possesses high surface hydrophilicity, chemical modifications have been applied to achieve the optimal surface properties to improve the performance of hydrogels for specific applications. Ideally, the effects of surface modifications would be stable, and the modification would not affect the inherent hydrogel properties. In recent years, a new type of surface modification has been discovered to be able to alter hydrogel properties by physically patterning the hydrogel surfaces with topographies. Such physical patterning methods can also affect hydrogel surface chemical properties, such as protein adsorption, microbial adhesion, and cell response. This review will first summarize the works on developing hydrogel surface patterning methods. The influence of surface topography on interfacial energy and the subsequent effects on protein adsorption, microbial, and cell interactions with patterned hydrogel, with specific examples in biomedical applications, will be discussed. Finally, current problems and future challenges on topographical modification of hydrogels will also be discussed.