In theory, you can usually tell the difference based on minor details such as their size. But there's considerable variation in fonts and handwriting, and because both ロ and 口 have the same stroke order they can look pretty similar, so in practice this can be difficult.
Luckily, you generally don't have to distinguish between them visually because you can almost always tell from context. For example, words like 出口 and 入り口 contain the kanji, and words like ゲロゲロ and ローマ contain the kana.
You can learn to read Japanese fairly well without necessarily being able to distinguish the two characters as written in your question title. (At least in the font I'm using, they're pretty hard to tell apart.)
In my opinion, the similar-looking ones you should learn to tell apart consistently are ones where the stroke order or position is different, like ン versus ソ, シ versus ツ, 人 versus 入, or 天 versus 夭, or the ones where the stroke lengths are different, like 土 versus 士, or 未 versus 末.