Protein metabolism is a dynamic physiological process governed by the balance between protein synthesis, degradation, and amino acid oxidation. This finely regulated system ensures maintenance of whole-body and skeletal muscle homeostasis and is profoundly influenced by hormonal signals. Anabolic hormones—including insulin, IGF-1, growth hormone, and androgens—promote protein synthesis and nitrogen retention, whereas catabolic hormones such as glucocorticoids, glucagon, and catecholamines stimulate proteolysis and amino acid oxidation. Insulin plays a central anabolic role primarily by suppressing protein degradation through inhibition of the ubiquitin–proteasome and autophagy–lysosome pathways, while its stimulation of protein synthesis is dependent on amino acid availability. Tissue-specific effects show that insulin robustly inhibits skeletal muscle proteolysis and has limited direct impact on muscle protein synthesis unless amino acids are concurrently supplied. Specific muscle protein fractions respond differently: insulin strongly stimulates mitochondrial protein synthesis, mildly affects myofibrillar proteins, and has intermediate effects on sarcoplasmic proteins. Other hormones like glucocorticoids exert potent catabolic effects by upregulating proteolytic pathways and inhibiting mTORC1 signaling, leading to muscle atrophy in chronic exposure. Androgens enhance muscle protein synthesis via androgen receptor-mediated activation of the IGF-1/PI3K/Akt/mTOR pathway, whereas estrogens provide protective effects by reducing oxidative stress and modulating protein turnover. Growth hormone and IGF-1 synergistically stimulate protein synthesis through mTORC1 activation. Glucagon indirectly promotes muscle proteolysis by increasing hepatic amino acid demand during gluconeogenesis. Myostatin acts as a key negative regulator, suppressing protein synthesis and stimulating proteolysis through Smad2/3 signaling. Collectively, hormonal regulation of protein metabolism integrates diverse anabolic and catabolic cues, determining muscle mass, metabolic health, and responses to physiological or pathological stress.