The low efficiency and stability of dye-sensitized solar cells (DSSCs) have remained the grand development challenges of this technology over the past 30 years. In this study, to increase the performance/cost ratio of DSSCs, we used several wild regional plants of the Persian Gulf zone for natural pigment production. Besides, co-sensitization and undoped and bio-Ca-doped TiO2 nanofibers were used as efficient strategies to improve and stabilize the DSSCs. Hence, in the first step, optimal conditions of pigment extraction were obtained using the response surface methodology (RSM) for both ordinary solvent extraction (SE) and microwave-assisted extraction (ME) methods. Then, the effectiveness of each pigment was evaluated as a sensitizer in natural DSSCs. After that, a comprehensive economic and profitability analysis was performed on both extraction methods. In the next step, the potential of the extracted natural dyes from Malva verticillata and Syzygium cumini was evaluated as mono and co-sensitizers in DSSCs. Finally, the potential of fabricated pristine and bio-Ca-doped TiO2 nanofibres was investigated as a novel and efficient photoanode for the DSSCs. Hence, the pristine and bio-Ca-doped TiO2 nanofibres were fabricated for mass production using a cost-effective and applicable electrospinning technique. Biocompatible calcium carbonate nanoparticles (bio-Ca) were synthesized from the cuttlebone of Sepia Pharaonis. The results show that the Microwave-assisted Malva verticillata-DSSC owned the highest energy conversion efficiency of 1.702% as well as the comparable open-circuit voltage to that of the reference DSSC that was made using synthetic sensitizer. Moreover, based on the photovoltaic results, the acidified cocktail-DSSCs and the bio-Ca-doped TiO2 nanofibres-based DSSCs could effectively improve and stabilize the DSSCs performance. Our results also demonstrated that the bio-Ca-doped TiO2 nanofibres-based DSSC retained about 78.38% of its initial efficiency af