Optimization of extraction parameters is crucial for maximizing the yield of the phytochemical content. The aim of this study was to optimize the extraction parameters for Nerium oleander (N. oleander) leaves, which is known for its anti-inflammation and pain alleviation properties. The actual yield in the extraction of N. oleander decreased with a decrease in polarity of the solvent with the exception of hexane. The highest yield was obtained with hexane (23.77%) and the lowest yield was obtained with ethyl acetate (7.36%). Methanol and acetone showed similarities in the yield, which were 20.81% and 20.89%, respectively. This similarity was attributed to their polarity index of 5.1. The water residue retained the highest filtrate, which accounted for possible loss of about 6.71% of the extract. Successive extraction of the same residue with solvent of varying polarities further improved the extract yield to between 9 and 36%. Phytochemical screening of the N. oleander extracts did not show any presence of alkaloids, anthraquinones and phlobatannins in all the extracts. Positive results for flavonoids were observed for the dichloromethane and chloroform extracts. No conclusive positive results for flavonoids were obtained for the extracts of water, methanol and hexane due to uncertainty in the observed colour changes. Negative results for flavonoids were revealed for the extracts of ethanol, acetone and ethyl acetate. Phytochemical screening revealed the presence of glycosides, phenols, tannins, steroids, terpenoids and saponins in all the extracts. However, the extracts of water, methanol, ethanol, acetone and hexane showed presented the most stable form, indicating the high concentration of saponins.