The Duchesnea genus (Rosaceae) is widely distributed throughout the world, and it is comprised of Duchesnea indica (D. indica) and Duchesnea chrysantha (D. chrysantha) species excluding varieties. The whole plant of Duchesnea genus has been used as a folk medicine for almost 2000 years in Asia. Its phytochemicals mainly include phenolic acids and their derivatives, flavonoids, terpenoids, tannins, lignins, sterols, among others. Modern pharmacological studies have shown that the Duchesnea genus exhibits a wide range of pharmacological effects, such as anticancer, antioxidant, anti-inflammatory, antiviral, antimicrobial activities, and so on. Nowadays, Duchesnea genus is mainly used in the treatment of various malignant tumors. However, its pharmacological activity research is mainly focused on plant extracts, while the pharmacological activities of its pure compounds, their mechanisms of action are seldom studied. Simultaneously, there is limited research on the synergistic effects of multiple effective parts, multiple components, and multiple targets. Additionally, there are few proprietary drugs mainly based on the Duchesnea genus, and their toxicity remains ambiguous. This review provides an overview of the phytochemical and pharmacological investigations of Duchesnea genus, and the applications of multi-target affinity ultrafiltration are prospected, aiming at providing further comprehensive information about the active compounds from Duchesnea genus for drug discovery and development. Synoptically, it is imperative and significant to clarify their toxicity, develop clinical preparations based on Duchesnea genus plants as a single drug or active ingredient, and strengthen the research on the synergistic effects of their multiple components, multiple targets, and multiple effective parts.