Manchester City have once again failed to advance past the quarter-final stage, being knocked out in the final eight in three successive seasons, but Guardiola believes the English side will eventually overcome this curse.
The Manchester-based club went into the game as huge favourites but Lyon once again caused an upset just like their group stage meeting last season.
Maxwell Cornet, who has now scored four times against City, drew first blood for the Ligue 1 side but Kevin De Bruyne brought the Englishmen level midway through the second half.
Substitute Moussa Dembele scored twice to inflict City’s third consecutive quarter-final defeat.
Speaking to the media after the game, the former Bayern Munich manager insisted that the Citizens’ bad luck in the Champions League will one day end.
"It is what it is. One day we will break the gap to the semi-finals," Guardiola told BT Sport.
"Second-half was okay, we were there, I had the feeling we were better, but you have to be perfect in this competition and we weren't.
"Sometimes you have to break this [barrier to the semis]. The team over last few years deserves it. Maybe one day we'll break this gap.”
Manchester City have never won the Champions League and have tasted continental success once when they hoisted the UEFA Cup Winners' Cup in 1970.
