Most of the synthetic drugs which induce side effect during overdose. The natural compounds are playing important role to reducing side effects of the synthetic drugs and also increase the immunity of recipients. The objective of the present study is to investigate the compatibility between Paracetamol as a synthetic compound with Spirulina as a natural compound.  The Paracetamol and Spirulina mixture were prepared in different ratio 1:1 (w/w) (Paracetamol: Spirulina), 1:2 (w/w) (Paracetamol: Spirulina) and 2: 1 (w/w) (Paracetamol: Spirulina). These samples were stored at different temperature (5 ˚C, 15 ˚ C, 30 ˚ C and 40 ˚ C) for one month. For every week samples were taken in the mixtures and the quantification of Paracetamol by using reversed phase liquid chromatography and estimation of chlorophyll A, B, total chlorophyll and total carotenoids in the mixture by using UV spectrophotometer. There was no significant loss of Paracetamol, chlorophyll, and carotenoids in their mixture. Both Paracetamol and Spirulina were stable under different temperature. Therefore it conclude that Paracetamol and Spirulina were compatible when mixed in a ratio of 1:1(w/w), 1:2 (w/w) and 2:1 w/w)