With the recent great progress made in flexible and wearable electronic materials, the upcoming next generation of skin-mountable and implantable smart devices holds extensive potential applications for the lifestyle modifying, including personalized health monitoring, human-machine interfaces, soft robots, and implantable biomedical devices. As a core member within the wearable electronics family, flexible strain sensors play an essential role in the structure design and functional optimization. To further enhance the stretchability, flexibility, sensitivity, and electricity performances of the flexible strain sensors, enormous efforts have been done covering the materials design, manufacturing approaches and various applications. Thus, this review summarizes the latest advances in flexible strain sensors over recent years from the material, application, and manufacturing strategies. Firstly, the critical parameters measuring the performances of flexible strain sensors and materials development contains different flexible substrates, new nano- and hybrid- materials are introduced. Then, the developed working mechanisms, theoretical analysis, and computational simulation are presented. Next, based on different material design, diverse applications including human motion detection and health monitoring, soft robotics and human-machine interface, implantable devices, and biomedical applications are highlighted. Finally, synthesis consideration of the massive production industry of flexible strain sensors in the future; different fabrication approaches that are fully expected are classified and discussed.