As personal portable devices, wearable sensors supply a leading-edge pathway to diagnose various diseases through actuating biological, physical, and chemical sensing capabilities. This could be commonly carried out via recording continuous and real-time of the patient's physiological statuses, as well as pathophysiological information. Although wearable sensor technology is in the infancy stage, tremendous attempts have been devoted to approaching flexible polymeric sensors. Among various polymer candidates applicable for synthesizing flexible and wearable sensors, the bio-based ones have piqued more interest due to their biocompatibility, biodegradability, eco-friendly features, and cost-effectiveness. Additionally, several fabrication techniques have been professed to architect efficient frameworks, such as films, hydrogels, aerogels, ferrogels, 3D layers, electrospun mats, and textiles. In this review, different mechanisms declared to engineer wearable sensors are overviewed. Then, regarding the advantages observed for bio-based polymers, the focused studies on the fabrication of natural-based wearable sensors are described. Notably, cellulose, chitosan, silk, gelatin, and alginate's role in sensing functionality is highlighted. Accordingly, this review has opened a new window to ahead opportunities for wearable sensors based on natural polymers. It is hoped that the new generation of sensors will be launched by combining emerging achievements obtained from employing sustainable and green elements and miniaturized sensor structures.