Hybrid microfluidic systems that are composed of multiple different types of substrates have been recognized as a versatile and superior platform, which can draw benefits from different substrates while avoiding their limitations. This review article introduces the recent innovations of different types of low-cost hybrid microfluidic devices, particularly focusing on cost-effective polymer- and paper-based hybrid microfluidic devices. In this article, the fabrication of these hybrid microfluidic devices is briefly described and summarized. We then highlight various hybrid microfluidic systems, including polydimethylsiloxane (PDMS)-based, thermoplastic-based, paper/polymer hybrid systems, as well as other emerging hybrid systems (such as thread-based). The special benefits of using these hybrid systems have been summarized accordingly. A broad range of biological and biomedical applications using these hybrid microfluidic devices are discussed in detail, including nucleic acid analysis, protein analysis, cellular analysis, 3D cell culture, organ-on-a-chip, and tissue engineering. The perspective trends of hybrid microfluidic systems involving the improvement of fabrication techniques and broader applications are also discussed at the end of the review.