The massive growth of potentially toxic cyanobacteria in water supply reservoirs, such as Legedadi Reservoir (Ethiopia), poses a huge burden to water purification units and represents a serious threat to public health. In this study, we evaluated the efficiency of the flocculants/ coagulants chitosan, Moringa oleifera seed (MOS), and poly-aluminium chloride (PAC) in settling cyanobacterial species present in the Legedadi Reservoir. We also tested whether coagulant-treated reservoir water promotes cyanobacteria growth. Our data showed that suspended solids in the turbid reservoir acted as ballast, thereby enhancing settling and hence the removal of cyanobacterial species coagulated with chitosan, Moringa oleifera seed, or their combination. Compared to other coagulants, MOS of 30 mg/L concentration, with the removal efficiency of 93.6%, was the most effective in removing cyanobacterial species without causing cell lysis. Contrary to our expectation, PAC was the least effective coagulant. Moreover, reservoir water treated with MOS alone or MOS combined with chitosan did not support any growth of cyanobacteria during the first two weeks of the experiment. Our data indicate that the efficacy of a flocculant/coagulant in the removal of cyanobacteria is influenced by the uniqueness of individual lakes/reservoirs, implying that mitigation methods should consider the unique characteristic of the lake/reservoir.