Abstract: In natural and agricultural ecosystems, many sessile organisms and plants often suffer from various biotic and abiotic stresses, such as the nutrient deficiency and heavy metal-caused nutrient disorder which hinder plant growth and development, and even affect crop productivity and reduce crop yield and quality seriously. Timely and efficient perception of nutrient status is critical for plant survival and reproduction. Under long-term natural selection, plants have evolved a complete set of molecular mechanisms to adapt to nutrient deficiency and heavy metal stress. Specific signals are formed to regulate or activate the gene expression, reprogramming of transcriptome, proteome, and metabolome, ultimately leading to physiological, biochemical, and phenotypic changes. The molecular mechanisms by which plants perceive nutrient signals have always been a hot research topic in the field of plant nutrition. Small peptides, generally less than 100 amino acids in length and involve in plant growth, development and bio-/abiotic stress responses, have been proved to be plant signal peptides by increasing evidence. This article reviewed the latest research progress on the regulation of nutrient signaling by endogenous small peptides in plant. The regulation of small peptides on the absorption and homeostasis of nitrogen, phosphorus, sulfate, and micronutrient like iron, as well as on the tolerance to the toxicity of heavy metals such as cadmium and arsenic was focused as typical cases. This article also proposed prospects of future research in this field.