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Plants have a life long association with human beings. Besides oxygen producing agents, plants are also a source of food, medicines and shelter. Cholistan desert rangeland in Pakistan is a hub of xerophytic plants with great traditional and medicinal value. The traditional and medicinal uses of Calligonum polygonoides were enlisted among the indigen of Cholistan desert. The local people (320 respondents) from 16 villages of four cholistani notified union councils were interviewed during household survey. Further, medicinal plant experts, manufacturers and herbal medicinal practitioners of the area were also interviewed. Results showed that local people used this shrub for its cooling properties (28.40 %), as general health tonic (7.50 %) and for treating malaria (1.30%). Medicinal plant experts claimed its remedial role against 10 diseases in different traditional recipes. Major diseases treated by using this shrub were spleen enlargement (35.70 %), diuretic (21.4%), fungal skin diseases (21.4%), stomach and intestinal pain (21.4%) and veterinary disease (7.1 %). Its use due to its cooling effect was only common use among both types of respondents. Different plant parts were also collected from Cholistan area for identification, proximate and secondary metabolite analysis. All parts found rich in carbohydrates as nitrogen-free extract (maximum in flowers i.e., 45.65%), crude protein (maximum in root barks i.e., 13%), crude fibre (maximum in leaves i.e., 34.21%), nitrogen (maximum in root bark i.e., 2.08 %) and ether extractable fat (maximum in flowers i.e., 6.6%). Presence of total phenolics, flavonoids and alkaloids in ample concentrations authenticated its effectiveness as medicine.