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For centuries, plants have been integral to traditional medicine, food preservation, and disease prevention. Chrozophora rottleri (Geiseler) A. Juss. ex Spreng., an annual herb of the Euphorbiaceae family, is widely used across India, Myanmar, Thailand, the Andaman Islands, and Malesia in various ethnomedicinal applications. This study aims to provide a comprehensive phytochemical profile and HPTLC analysis of Chrozophora rottleri leaves to highlight its medicinal potential. The leaves were subjected to hot continuous extraction using a Soxhlet apparatus with solvents of increasing polarity to maximize the yield of bioactive compounds. Phytochemical screening identified the presence of alkaloids, flavonoids, tannins, saponins, glycosides, triterpenoids, phenols, steroids, coumarins, cardiac glycosides, and phytosterols in different extracts. Quantitative analysis revealed that alkaloids were most abundant in chloroform and ethanol extracts (500 mg/g), while flavonoids were prominent in ethyl acetate and ethanol extracts (200 mg/g). Phenols and tannins were concentrated in ethyl acetate and aqueous extracts (200 mg/g). The HPTLC analysis displayed distinct separation of phytochemical bands at varying retention factor (Rf) values, using toluene: ethyl acetate (9:1 v/v) at 254 nm and a combination of ethyl acetate: water: formic acid: glacial acetic acid (100:26:11:11 v/v/v/v) at 366 nm and 540 nm. Chromatograms revealed multiple peaks, signifying a rich diversity of bioactive compounds. These findings support the traditional uses of Chrozophora rottleri and underscore its potential for further pharmacological research. The research concluded that the leaf extract of Chrozophora rottleri is abundant in various phytochemicals, potentially contributing to its therapeutic properties. Further investigation into its individual phytochemical profile is recommended for isolating novel compounds. High-performance thin-layer chromatography (HPTLC) fingerprint analysis of Chrozophora rottleri leaf extract could serve as a reliable method for precise plant identification, acting as both a phytochemical marker and a valuable indicator of genetic variability within plant populations.