In the present work, the competitive host-guest interaction between amantadine (AMD), ferrocene (Fc), and cucurbit[7]uril (Q[7]) was adopted to fabricate an "off-on-off" mode sensor. Firstly, strong anodic Ru(bpy)32+ electrochemiluminescence (ECL) was obtained at a MoS2 nanosheet (MoS2NS) modified electrode without the need of additional coreactant due to the excellent electrocatalytic behavior of MoS2NS. Then, Fc was used to inhibit ECL signal via electron transfer process between Ru(bpy)32+ and Fc. In the presence of Q[7], Fc was accommodated into its cavity, leading to the recovery of ECL signal. AMD exhibited stronger combining ability with Q[7] than Fc, and could replace Fc from the cavity of Q[7], leading to the inhibited ECL intensity again. The variation of ECL intensity changed linearly with AMD concentration. Therefore, an ECL sensor for the quantitative detection of AMD was proposed based on host-guest interaction of Q[7]. Under the optimal conditions, AMD can be detected in the range of 1 nM to 50 nM whit a detection limit of 0.27 nM (3 sigma). Importantly, the proposed sensor has outstanding specificity and accuracy, indicating that cucurbit[n]urils have potential applications in ECL sensing field through the host-guest interaction.