This study was designed to investigate the acute toxicity (mortality) and sublethal effects (fertility and potential natality) of carlina oxide, the main constituent of Carlina acaulis essential oil (EO), against adults of Metopolophium dirhodum (Walker) (Hemiptera: Aphididae). Moreover, its toxicity was evaluated against two aphid natural enemies, i.e., Aphidoletes aphidimyza Rondani (Diptera: Cecidomyiidae) and Chrysoperla carnea Stephens (Neuroptera: Chrysopidae). The highest tested concentration (3.0 mL L−1) resulted in 96.7% mortality of adults of the target pest, highlighting that this concentration of carlina oxide had a similar effectiveness as the positive control we used. Furthermore, probit analysis allowed the estimation of a LC50 of 1.06 mL L−1 and a LC90 of 2.58 mL L−1 for the target pest, which resulted in a much higher mortality rate than that found on natural enemies, i.e., A. aphidimyza (6.7 ± 4.7% ± SD when exposed to the aphid LC90) and C. carnea (7.0 ± 5.5% ± SD when exposed to the aphid LC90), showing the limited non-target impact of carlina oxide. The use of LC30 and LC50 of this compound allowed the fertility inhibition of the target pest by 35.68 ± 6.21% and 23.66 ± 10.58%, respectively, and potential natality inhibition of the target pest by 52.78 ± 4.48% and 59.69 ± 5.60%, respectively. Of note, carlina oxide showed excellent insecticidal activity against M. dirhodum, comparable to the commercial insecticide considered. Overall, the low toxicity of carlina oxide toward A. aphidimyza and C. carnea makes it a safe compound for non-target organisms as well as suitable for developing a green insecticide for the management of M. dirhodum and perhaps other insects of agricultural or medical and veterinary interest.