Polarity control of two-dimensional (2D) materials is of great significance for high-performance electronics and optoelectronics. Organic molecules, with designable structures, provide an effective tool to precisely modulate the polarity of 2D materials through non-covalent or covalent interactions, further influencing the 2D materials’ photoelectric properties. In this review, we summarize the interaction mechanisms between organic molecules and 2D materials, demonstrating the significant changes of electronic structures and the modulation of the carrier type and concentration. In addition, we introduce the applications of organic molecule engineering for various 2D devices and discuss both the current opportunities and challenges for better research in the future.