Bri1-EMS Suppressor 1 (BES1) and Brassinazole Resistant 1 (BZR1) are two key transcription factors in the brassinosteroid (BR) signaling pathway, serving as crucial integrators that connect various signaling pathways in plants. Extensive genetic and biochemical studies have revealed that BES1 and BZR1, along with other protein factors, form a complex interaction network that governs plant growth, development, and stress tolerance. Among the interactome of BES1 and BZR1, several proteins involved in posttranslational modifications play a key role in modifying the stability, abundance, and transcriptional activity of BES1 and BZR1. This review specifically focuses on the functions and regulatory mechanisms of BES1 and BZR1 protein interactors that are not involved in the posttranslational modifications but are crucial in specific growth and development stages and stress responses. By highlighting the significance of the BZR1 and BES1 interactome, this review sheds light on how it optimizes plant growth, development, and stress responses.