Brassinosteroids (BRs) are known as the sixth type of plant hormone participating in various physiological and biochemical activities and play an irreplaceable role in plants. Small-molecule compounds (SMCs) such as nitric oxide (NO), ethylene, hydrogen peroxide (H2O2), and hydrogen sulfide (H2S) are involved in plant growth and development as signaling messengers. Recently, the involvement of SMCs in BR-mediated growth and stress responses is gradually being discovered in plants, including seed germination, adventitious rooting, stem elongation, fruit ripening, and stress responses. The crosstalk between BRs and SMCs promotes plant development and alleviates stress damage by modulating the antioxidant system, photosynthetic capacity, and carbohydrate metabolism, as well as osmotic adjustment. In the present review, we try to explain the function of BRs and SMCs and their crosstalk in the growth, development, and stress resistance of plants.