Irresponsible human interventions, encroachment of natural habitats, and climate change negatively affect wildlife. In this study, the effects of human influence on Wadi Hagul, an unprotected area in the north of the Egyptian Eastern Desert that has recently been subjected to blatant encroachments of vegetation, were studied. The most important of these threats is the construction of the new road Al-Galala–Wadi Hagul–Zafarana. In Wadi Hagul, 80 species are reported in this study; the most represented plant families are Asteraceae (15 species) and Brassicaceae (6 species). Perennial, chamaephyte and Saharo-Arabian species were recorded in the highest percentage. Detrended canonical correspondence analysis showed that latitude, longitude, altitude, silt, sand contents, pH, and CO32− content are the factors that have the highest effect on vegetation distribution in the studied stands. Several invasive and alien species such as Euphorbia prostrata have been listed; these species typically have a negative effect on native species. The Soil Adjusted Vegetation Index (SAVI) indicated a decrease in plant cover during the study period, as compared to previous years. In 2013 and 2020, SAVI ranged from −0.02 to 0.42 and from −0.18 to 0.28, respectively. Recently, the violation and destruction of wildlife have increased, therefore, preserving it along with general biodiversity has become an urgent necessity.