In this paper, we propose a “casting” strategy to prepare intrinsically fluorescent, uniform and porous gelatin microgels with multi-responsiveness. Gelatin microgels with tunable size were obtained by copying the structure of a porous CaCO3 template. The diameter of the gelatin microgels was sensitive to salt concentration and pH. Doxorubicin and Rhodamine B as model drugs were loaded into the microgels via electrostatic interaction and release of the payload was triggered by changing the salt concentration and pH, respectively. Cell experiments demonstrated that the gelatin microgels had an excellent biocompatibility and biodegradability. The merits of gelatin microgels such as tunable size, biocompatibility, and stimulus responsive upload and release of positively charged small molecules will permit the microgels as excellent carriers for drug delivery. The whole manufacturing process is furthermore environmental-friendly involving no organic solvents and surfactants.