Replacing a portion of ordinary Portland cement (OPC) with natural pozzolans may be an effective solution to reduce the carbon footprint of the concrete industry and construction costs, and to improve concrete durability in general terms. However, some natural pozzolans, such as perlite, need to be pretreated to be reactive enough and satisfy the minimum standard qualifications of the concrete industry. This research investigated the effectiveness of milling of natural perlite as an alternative to calcination, which is the more common reactivation method. For this purpose, the effects of replacing OPC with natural perlite powder (NPP) were studied at three different levels of fineness and replacement ratios. A variety of tests for the mechanical and transport properties of the concrete were carried out, including a compressive strength test, a surface electrical resistivity test, a water penetration test, a rapid chloride permeability test, and a rapid chloride migration test. These tests conducted on 14 different types of concrete mixtures with various ratios of water-to-cementitious materials (W/Cm), cement content, and replacement ratios. The results demonstrated that increasing the fineness of natural perlite could be an effective method to reactivate NPP, leading to almost the same compressive strength while improving the transport properties significantly.