The fluorescent silk fibroin (FSF) is useful in a number of biomedical applications. However, some FSFs are less useful for medical applications because they are derived from toxic compounds. Here we report for the first time a fast (∼20 min), ultrasonic assisted, eco-friendly synthesis of four fluorescent organotin Schiff compounds using the corresponding aldehyde, benzoic hydrazide, and diorganotin oxide ( 1 : MeO-L-SnPh 2 , 2 : t Bu 2 -L-SnPh 2 , 3 : HO-L-SnPh 2 , and 4 : HO-L-SnBu 2 ). These compounds were fully characterized by NMR spectroscopy ( 1 H, 13 C, and 119 Sn), HRMS, and UV/Vis and fluorescence spectroscopy. Single crystal X-ray diffraction investigations of complexes 1 and 2 are also reported. The as-prepared organotin Schiff compounds exhibit fluorescence at ambient temperature with good photophysical properties (fluorescence quantum yields Φ : 18–55%). These organotin compounds serve as fluorescent dyes in silk fibroin ( Bombyx mori ). The organotin dyed fluorescent silk fibroin showed a uniform staining, high viability, and good capacity to retain organotin compounds which might be used as innocuous scaffolds in tissue engineering.