Eleusine indica is a highly competitive and difficult-to-control plant in annual and perennial crops. In Colombia, broad-spectrum herbicides, such as paraquat and glyphosate, have begun to present poor levels of control for this weed. The multiple resistance to glyphosate and paraquat, the increase in herbicide performance with adjuvants (Retenol® and Trend® 90), and alternative herbicides were evaluated in a resistant (R) population of E. indica collected in rice fields, which is rotated with herbicide-resistant (HR) crops. Based on plant mortality, the R population was 9.8 and 7.2 times more resistant than susceptible (S) plants to glyphosate and paraquat, respectively. R plants accumulated 4.2 less shikimic acid and had at least 70% less electrolyte leakage than S plants when they were exposed to glyphosate and paraquat, respectively. Both adjuvants increased the foliar retention of herbicides. In addition, adjuvants also increased the performance of glyphosate effectiveness between 22% and 58% and that of paraquat from 61% to 100%. Alternative herbicides (atrazine, clethodim, imazamox, diuron, flazasulfuron, glufosinate, oxyfluorfen, quizalofop, and tembotrione) provided high levels of control in both populations of E. indica. This is the first case of multiple resistant E. indica confirmed in Colombia. Adjuvants improved the leaf retention and efficacy of glyphosate and paraquat. In summary, the alternative herbicides evaluated in this study should be adopted by Colombian farmers and provide additional herbicide modes-of-action to combat future resistance.