区别在于具体含义用法的不同。
1、表示对某人感到失望，通常用介词with, in，不可用at。
例句：
①Castle-hunters won't be disappointed with the Isle of Man.
马恩岛不会让城堡探寻者失望的。
②I must admit that I'm very disappointed in you.
我必须承认，我对你非常失望。
2、表示对某事感到失望，一般用介词at,with，也可用about，但不可用in。
例句：
①He is not disappointed at the failure to make headway towards resolving their differences.
他们之间的分歧依然未能解决，他对此并不感到沮丧。
②He was disappointed at the result.
他对这样的结果感到失望。
③Are you very disappointed about losing the race?
你是否对在比赛中失利很失望？
3、表示对某一行为感到失望，通常用介词at, about，不可用with,in。
例句：
①Pardew said: He went straight home after the game and I am very disappointed about that.
帕度说我对他直接离场回家的作法感到失望。
②He was really disappointed about at not being able to go.
他未能去成感到失望。
区别：
be disappointed at后面接sth(或doing sth)，指对某一事实或情况（或某一行为）感到失望；
be disappointed in后面接sb ，指对某人（或某一事实或情况）感到失望；
be disappointed with 后面接sb，对某人（或某一事实或情况）失望。
be disappointed at：指对某一事实或情况（或某一行为）感到失望
例句：
（1）You must be disappointed at the first sight of me, I guess.
所以我相信同学们看到我的第一眼一定感到非常的失望。
（2）I have never said that I would be disappointed if I remained at Sevilla, I know that here there are many people who appreciate me and I am relaxed.
我从未说过如果留在塞维利亚我会感到很失望，我知道这里有很多人很赏识我，因此留在这里我也会感到很轻松。
（3）I told them that they would be disappointed at the news.
我告诉他们，听到这个消息，他们会失望的。
（4）You must be disappointed at losing the chance.
失去这次机会，你肯定很失望吧。
（5）Benitez said: "You have to be disappointed because it's a draw at home but the performance ofthe team was again pretty good, for me."
贝尼特斯说道：“你一定很失望，因为主场战成平局，但是对我来说，球队踢了一场精彩的比赛。”
be disappointed in：指对某人（或某一事实或情况）感到失望
例句：
（1）You may find them too slow or soft for your tastes and be disappointed in the real thing.
对你的喜好而言，你可能发觉它们太缓慢或者柔软，然后在真枪实弹中失望。
（2）For all their efforts, those seeking to mass-produce children in this way, as well as others whoseek an exact copy of someone else, would almost certainly be disappointed in the end.
对于那些寻求以此种方式大批量生产孩子的人，或者对于那些想复制他人的人来说，他们的一切努力最终会让他们失望的。
（3）My parents will be disappointed in me if I fail in the exam.
如果我考试不及格，我父母将为我感到失望。
（4）If you do this many people will be disappointed in you.
你这样下去很多人都会对你失望的。
（5）If I quit now, I'll be very disappointed in myself later this afternoon.
如果现在退出，那下午我会觉得非常后悔。
be disappointed with ：对某人（或某一事实或情况）失望
例句：
（1）If they have not done so then they may be disappointed with the impact of their R&D spend oninnovation. 如果它们没有这样做，那么它们可能对它们在研发上的开支对创新形成的影响感到失望。
（2）The protesters will most likely be disappointed with his speech to the Syrian parliament.
抗议者或对他向叙利亚议会的讲话感到非常失望。
（3）"They're not going to be disappointed with that, " says Dalton , also a professor at Ohio State University.
“他们不会被轻易失望， ”说，多尔顿，也任教于俄亥俄州立大学。
（4）You won't be disappointed with this 21st-century adaptation.
你不会失望，这与21世纪的适应。
（5）I can't be disappointed with myself, I have to be stronger.
我不能对自己失望，我要坚强起来。