Due to the quantum size effect and other unique photoelectric properties, quantum dots (QDs) have attracted tremendous interest in nanoscience, leading a lot of milestone works. Meantime, the scope and scientific connotation of QDs are constantly expanding, which demonstrated amazing development vitality. Besides the well-developed Cd-containing II–VI semiconductors, QDs of environmentally friendly I–III–VI (I = Cu, Ag; III = Ga, In; VI = S, Se) chalcogenides have been a hot spot in the QDs family, which are different from traditional II–VI QDs in terms of multi-composition, complex defect structure, synthetic chemistry and optical properties, bringing a series of new laws, new phenomena and new challenges. The composition of I–III–VI chalcogenides and their solid solutions can be adjusted within a very large range while the anion framework remains stable, giving them excellent capability of photoelectric property manipulation. The important features of I–III–VI QDs include wide-range bandgap tuning, large Stokes shift and long photoluminescence (PL) lifetime, which are crucial for biological, optoelectronic and energy applications. This is due to the coexistence of two or more metal cations leading to a large number of intrinsic defects within the crystal lattice also known as deep-donor-acceptor states, besides the commonly observed surface defects in all QDs. However, a profound understanding of their structure and optoelectronic properties remains a huge challenge with many key issues unclear. On one hand, the achievements and experience of traditional QD research are expected to provide vital value for further development of I–III–VI QDs. On the other hand, the understanding of the emerging new QDs, such as carbon and other 2D materials, are even more challenging because of the dramatically different composition and structure from II–VI semiconductors. For this, I–III–VI QDs, as a close relative to II–VI QDs but with much more complex composition and structure variation, provide a great opportunity as a gradual bridge to make up the big gap between traditional QDs and emerging new QDs, such as carbon dots. Here, we hope to compare the research progress of I–III–VI QDs and II–VI QDs, in an effort to comprehensively understand their structure, synthetic chemistry, optical electronic and photocatalytic properties. We further give insights on the key potential issues of I–III–VI QDs from the perspective of bridging between traditional QDs and emerging carbon dots, especially the profound principles behind synthetic chemistry, PL mechanism and optoelectronic applications.