The innovative design of natural scaffolds and biomaterials to drive a desired cellular response is of great importance for the advancement of present-day tissue engineering. Decellularized extracellular matrices, biopolymer scaffolds, and extracellular matrix-inspired polymers have shown promising potential for directing cellular behaviors to promote regeneration by means such as cellular alignment, enhanced proliferation, and directed differentiation. A variety of naturally derived and inspired polymeric scaffoldings fabricated in combination with organic materials that include a multitude of micropatterning processes to direct cell function are outlined herein. The current methods for the development of micropatterned biomatrices are specific to the materials at hand and can be categorized as follows: (1) additive manufacturing, (2) instability-induced surface micropatterning, (3) patterning by dewetting, (4) patterning by evaporation, and (5) patterning by electric field and thermal gradient. Although these techniques appear to be mainly tailored toward polymeric substances, the science behind these applied processes is rooted within nature. The responsive cellular performances and cell-material interactions are also explored, focusing on the topography of the material’s surface for cellular guidance and the resulting cellular behaviors specifically cell morphology and gene and protein expression.