Against the backdrop of global climate change mitigation and the accelerating transition toward low-GWP refrigerants, research on alternative refrigerants for variable refrigerant flow (VRF) systems has emerged as a critical focus in refrigeration and air conditioning. This paper presents a comprehensive review of recent advances in low-GWP refrigerant replacement technologies for VRF systems. A three-dimensional analytical framework encompassing "policy-performance-technology" was developed to systematically evaluate the influence of regulatory policies in major global economies on technological pathways and to assess the thermophysical properties of alternative refrigerants such as R32 and R454B. The findings indicated that R32 offered a 2.1%-10.2% improvement in energy efficiency compared with R410A although stricter control measures were required because of its A2L flammability classification. In contrast, low-GWP refrigerants, such as R454C, met environmental requirements but resulted in a 5.9%-7.6% decline in energy efficiency. Key technological breakthroughs were reviewed, including compressor optimization, lubricant management, and long-distance refrigerant distribution. Special emphasis was placed on safety-enhancing solutions such as intelligent refrigerant charge diagnostics based on deep learning and the application of secondary loop systems to reduce the charge of flammable refrigerants. To address the challenges related to material compatibility and system integration, a phased implementation roadmap was proposed. This review provided a systematic theoretical foundation for the low-carbon transition of the VRF industry and offered valuable insights for future policymaking and technology development.