Industries such as hotels, pharmaceuticals, dairy and food and beverage units require heating and cooling for their functional requirements. These industries mostly use fossil fuel-fired boilers for heating (hot water at 60 to 90 °C) and vapor compression refrigeration systems for cooling (-30 to 5 °C), which results in higher primary energy consumption and CO2 emissions. Heat pumps (HPs) are a sustainable option for meeting the simultaneous heating and cooling demands. However, these use synthetic refrigerants with high global warming potential (GWP). Therefore, this research aims to evaluate the potential of low and medium-temperature HPs using low GWP refrigerants such as R744, R290, R600a, R161, R1234yf, R1234ze(E) and R1233zd(E). The best refrigerant for the HPs is proposed based on energy efficiency, environmental impact and economic feasibility as critical factors, compared with the conventional high GWP refrigerant (R134a). The occurrence of pinch points across the gas cooler/condenser is evaluated in the analysis. Rummy cycle climate performance (LCCP) is assessed to study the environmental impact. Also, the operating costs of these HPs are estimated and compared with the conventional systems used in the industry. Results show that R744 HP is an energy-efficient and clean solution for simultaneous heating and cooling applications, primarily at higher temperature lift (lower Tw,i and higher Tw,o) conditions.