Amphoteric functional polymers containing anionic and cationic groups have the advantages of pH‐responsive function, self‐assembly, and anti‐polyelectrolyte effect, which have been diffusely applied in the healthcare industry, leather area, and so forth. Very recently, with the development of organic chrome‐free tanned ecological leather manufacturing technology, the anionic retanning and fatliquoring agents for traditional chrome tanning system have gradually lost their dominant position due to the weak interactions between positively charged collagen fibers and negatively charged wet finishing auxiliaries, resulting in a series of problems such as low dye uptake, uneven dyeing, and so forth. To address this issue, recent researches have been devoted to developing amphoteric polymers for leather retanning and fatliquoring processes. In this review, we give a comprehensive overview of the preparation and application of amphoteric materials for leather retanning and fatliquoring agents. With the perspective of their properties, current challenges, and outlook in the future, crafting functional and environmentally friendly amphoteric materials are further put forward. The development and application of amphoteric polymer wet finishing auxiliaries will greatly promote the integrated manufacturing of ecological leather, and further motivate the upgrading, transformation, and sustainable development of the traditional leather industry.