The advent of the novel in-sensor/near-sensor computing paradigm significantly eliminates the need for frequent data transfer between sensory terminals and processing units by integrating sensing and computing functions into a single device. This approach surpasses the traditional configuration of separate sensing and processing units, thereby greatly simplifying system complexity. Two-dimensional materials (2DMs) show immense promise for implementing in-sensor computing systems owing to their exceptional material properties and the flexibility they offer in designing innovative device architectures with heterostructures. This review highlights recent progress and advancements in 2DM-based in-sensor computing research, summarizing the unique physical mechanisms that can be leveraged in 2DM-based devices to achieve sensory responses and the essential biomimetic synaptic characteristics for computing functions. Additionally, the potential applications of 2DM-based in-sensor computing systems are discussed and categorized. This review concludes with a perspective on future development directions for 2DM-based in-sensor computing.