Climate indices are developed to determine climate impacts on different socioeconomic sectors, providing a comprehensive communication of complex information arising from climate change assessments. These may be used by decision-makers to properly and timely implement climate change adaptation measures in different sectors of human activity, such as agriculture and crop selection, forest, and coastal management, among others. Here, we present a comprehensive analysis of climate indices estimated for Portugal, known to be in a climate change hotspot. A multi-variable 13-member ensemble of EURO-CORDEX Regional Climate Model simulations is used to assess future climate change projections of climate indices, exploring three future scenarios until 2100, and considering three different emission scenarios, namely the RCP2.6, RCP4.5 and RCP8.5. Aligned with warming and drying projected conditions, an increase in the number of summer days to very hot days is expected to become more frequent and intense, with more impact over interior regions. Tropical nights are projected to become more common, affecting the thermal comfort conditions and threatening future human health. Although the future projections show an overall reduction in the number of wet days, the amount of precipitation during short-time wet periods will increase leading to an intensification of moderate/heavy rainfall. These results corroborate that Portugal is in a climate change hotspot, calling for efficient policymaking by the relevant authorities. Indeed, such projections call for an urgent planning and development of adaptation measures to safeguard critical sectors of the Portuguese society, such as agriculture, forests, coastal management, among others.